RU2024493C1 - Process for preparing isomers, or pharmaceutically acceptable salts, and aldehyde as an intermediate product in the 1-alkyl, 1-alkenyl or 1-alkynylaryl-2-amino-1, 3- propanediol system - Google Patents

Abstract

FIELD: used as antiphlogistics. SUBSTANCE: in order to prepare 1-alkynylpyridinyl-2- amino-1, 3-propanediol, pyridinylcarboxaldehyde is condensed with amidomalonic acid ester, followed, if necessary, by hydrogenation or hydrolysis of the resulting product. EFFECT: improved properties of the resulting product. 3 cl

Description

O

S

O
R₅ -CH₃(CH₂)_m C≡C,
CH₃(CH₂)_mCH=CH-, CH₃(CH₂)_mCH₂-CH₂-,

-CH₂(CH₂)_nC

C-,

-CH₂(CH₂)_n CH= CH или

-CH₂(CH₂)_n CH₂-CH₂-, где m = 3-15; n = 0-12;
R₁ - водород или

R₆, где R₆ - водород, алкил, алкокси, или OCH₂-

;
R₂ - водород или алкил;
R₃ - водород, алкил или

R₆, где R₆ - определен выше, R₄ -

OR₇, где R₇ - водород или алкил, или СН₂OR₈, где R₈ - водород или

R₆, где R₆ - определен выше,
R₁ и R₈, взятые вместе с атомом кислорода, с которым они связаны, образуют группу формулы

где R₉ и R₁₀ независимо являются водородом или алкилом.The invention relates to 1-alkyl, 1-alkenyl or 1-alkynaryl-2-amino-1,3-propanediolam of the formula I
RCH (OR ₁ ) CHN (R ₂ R ₃ ) P ₄ where

O

S

O
R ₅ -CH ₃ (CH ₂ ) _m C≡C,
CH ₃ (CH ₂ ) _m CH = CH-, CH ₃ (CH ₂ ) _m CH ₂ -CH ₂ -,

-CH ₂ (CH ₂ ) _n C

C-

-CH ₂ (CH ₂ ) _n CH = CH or

-CH ₂ (CH ₂ ) _n CH ₂ -CH ₂ -, where m = 3-15; n is 0-12;
R ₁ is hydrogen or

R ₆ , where R ₆ is hydrogen, alkyl, alkoxy, or OCH ₂ -

;
R ₂ is hydrogen or alkyl;
R ₃ is hydrogen, alkyl or

R ₆ , where R ₆ is as defined above, R ₄ is

OR ₇ , where R ₇ is hydrogen or alkyl, or CH ₂ OR ₈ , where R ₈ is hydrogen or

R ₆ , where R ₆ is as defined above,
R ₁ and R ₈ taken together with the oxygen atom to which they are bonded form a group of the formula

where R ₉ and R ₁₀ are independently hydrogen or alkyl.

 The invention also relates to the optical isomers of these compounds or their pharmaceutically acceptable salts, as well as the use of these compounds for the treatment of inflammatory conditions (since they have the ability to inhibit protein kinase C), for the treatment of psoriasis and other skin diseases, for the treatment of cancer (since these compounds have the ability to inhibit the growth of tumor cells), for the treatment of memory disorders, for example, such as Alzheimer's disease, as well as anti ibic and antibacterial agents that can be used both separately and in combination with adjuvants.

R₅;
R₁, R₂ и R₃ - водород и R₅ - СН₃(СН₂)_mСН₂=СН₂ или

CH₂(CH₂)_nCH₂= CH₂. Предпочтительными также являются соединения, где R представляет собой

; R₁ и R₂ - водород; R₄-

; R₅ - CH₃(CH₂)_mC≡C.Preferred 2-amino-1,3-propanediols of the present invention are compounds in which

R ₅ ;
R ₁ , R ₂ and R ₃ are hydrogen and R ₅ is CH ₃ (CH ₂ ) _m CH ₂ = CH ₂ or

CH ₂ (CH ₂ ) _n CH ₂ = CH ₂ . Also preferred are compounds wherein R is

; R ₁ and R ₂ are hydrogen; R ₄ -

; R ₅ - CH ₃ (CH ₂ ) _m C≡C.

, где R₅ - CH₃(CH₂)_m C≡C.The invention also relates to compounds of the formula R ₁ CHO (1a), where

where R ₅ is CH ₃ (CH ₂ ) _m C≡C.

, где m = 3 - 15, n = 0 - 12, которые используются в качестве промежуточных соединений для получения 2-амино-1,3-пропандиолов.CH ₃ (CH ₂ ) _m CH = CH, CH ₃ (CH ₂ ) _m CH ₂ CH ₂ or

where m = 3-15, n = 0-12, which are used as intermediates for the preparation of 2-amino-1,3-propanediols.

 The term "alkyl", as used in the description and claims, refers to a straight or branched hydrocarbon radical which is not unsaturated and has 10 carbon atoms. Examples of alkyl groups are methyl, ethyl, 1-propyl, 2-propyl, 1-butyl, 1-pentyl, 3-hexyl, 4-heptyl, 2-octyl, 3-nonyl, 4-decyl and the like. The term "alkanol" refers to a compound formed by combining an alkyl group and a hydroxyl radical. Examples of alkanols are methanol, ethanol, 1- and 2-propanol, 2,2-dimethylethanol, hexanol, octanol and the like. The term "alkanoic acid" refers to a compound formed by combining a carboxyl group with a hydrogen atom or an alkyl group. Examples of alkanoic acids are formic acid, acetic acid, propanoic acid, 2,2-dimethylacetic acid, caproic acid, octenoic acid, decanoic acid, etc. The term "halogen" refers to a group of compounds including fluorine, chlorine, bromine and iodine . The term "alkanoyl" refers to a radical formed by removal of a hydroxyl group from alkanoic acid. Examples of alkanoyl groups are formyl, acetyl, propionyl, 2,2-dimethylacetyl, hexanoyl, octanoyl, decanoyl, and the like. The term "lower" can be applied to any of these groups having a carbon skeleton and containing no more than 8 carbon atoms.

 Compounds of the present invention, in which there is no symmetry element, exist as optical antipodes and their racemic forms. Optical antipodes can be obtained from the corresponding racemic forms using standard optical resolution techniques, including, for example, the separation of diastereometric salts of compounds that are characterized by the presence of a basic amino group and an optically active acid, or compounds that are characterized by the presence of a carboxylic acid group and an optically active base, or by synthesis from their optically active precursors.

 The present invention includes all optical isomers, their racemic forms and geometric isomers, which will be disclosed in the description and claims. Formulas of the compounds presented in the present description show that they include all possible geometric and optical isomers.

и замещение аминогруппы трео-2-амино-1,3-пропандиола (9с) настоящего изобретения гидроксильной группой образует энантиомер (9d), в котором элемент симметрии во всех конформациях, один из которых представлен формулой 9d

Новые 1-алкил-, 1-алкенил- и 1-алкиниларил-2-амино-1,3-пропандиолы настоящего изобретения могут быть получены способами, проиллюстрированными в реакционных схемах А, В и С для ряда пиридинов, имеющих аралкильную боковую цепь. Указанные трансформации могут быть использованы при получении соединений настоящего изобретения, в которых арильной группой, среди прочих, является замещенный и незамещенный фенил, фурил, тиенил, изоксазолил, изотиазолил, и пирролил, тиазолил, и оксазолил, имеющий 1-алкильную, 1-алкенильную или 1-алкинильную боковую цепь.Compounds of the present invention having adjacent chiral centers are present as diastereomers and differ as erythro and threo isomers. Erythro diastereomers are also compounds that can become a mesoform, i.e. optically inactive form, due to the fact that they have a symmetry element in one of the possible conformations, if one of the unequal substituents is replaced by one another. Treo-diastereomers are those compounds that remain the enantiomer, i.e. optically active isomer, due to the absence of a symmetry element in one of the possible conformations, if one of the unequal substituents is replaced by the other. For example, the substitution of the amino group of the erythro-2-amino-1,3-propanediol (9a) of the present invention with a hydroxyl group forms a meso-1,2,3-propanetriol (9b) having a plane of symmetry passing through the carbon skeleton of the molecule, as shown below

and the substitution of the amino group of the threo-2-amino-1,3-propanediol (9c) of the present invention with a hydroxyl group forms the enantiomer (9d), in which the symmetry element in all conformations, one of which is represented by formula 9d

The novel 1-alkyl-, 1-alkenyl- and 1-alkynylaryl-2-amino-1,3-propanediols of the present invention can be prepared by the methods illustrated in Reaction Schemes A, B and C for a series of pyridines having an aralkyl side chain. These transformations can be used in the preparation of compounds of the present invention in which the aryl group, among others, is substituted and unsubstituted phenyl, furyl, thienyl, isoxazolyl, isothiazolyl, and pyrrolyl, thiazolyl, and oxazolyl having 1-alkyl, 1-alkenyl or 1-alkynyl side chain.

To obtain 1-alkynylpyridinyl-2-amino-1,3-propanediol (7), where W and X are hydrogen, alkyl, alkoxy, halogen or trifluoromethyl, pyridinylcarboxaldehyde (2), in which W and X are defined above, and Y is halogen, condensed with an amidomalonic acid ester (3), where R ₁₁ and R ₁₂ are alkyl, in order to obtain pyridinyl propionate (4), where R ₁₁ and R ₁₂ , X and Y are as defined above, which are alkynylated to give alkynyl pyridine (5) where R ₁₁ and R _12, W and X are as defined above, n = 3-15, which, in turn, reduced to pyridinyl-1,3-propanediol (6) rk R _12, W and X are as defined above, and then hydrolyzed to the compound (7).

The condensation of carboxaldehyde (2) and malonate (3) is carried out in an ethereal solvent in the presence of a tertiary amine. Examples of such solvents can be diethyl ether, 1,2-dimethyloxyethane, 2-methoxyethyl ether, dioxane and tetrahydrofuran. Examples of tertiary amines are pyridines (pyridine, picoline, lutidine and collidine) and trialkylamines (trimethylamine, triethylamine, tripropylamine). Tetrahydrofuran is the preferred solvent, and triethylamine is the preferred tertiary amine. Since the condensation temperature is not critical, then the reaction is preferably carried out at about room temperature (25 ° ^C), although said reaction can occur both at reduced temperatures (about 0-25 ° ^C) and elevated temperatures (about ²⁵ ° C to the boiling point of the reaction mixture).

где W и n определены выше, в акцепторе кислоты, например, ди- или триалкиламино, таком, как диэтиламин, дипропиламин, триметиламин, или трипропиламин, и в присутствии дихлорида бис(трифенилфосфин) палладия/иодида меди при температуре около 0-75^оС. Предпочтительным акцептором кислоты является триэтиламин. Предпочтительной температурой алкилирования является температура около 50-60^оС. При этом может быть использован эфирный растворитель. Такими эфирными растворителями являются диэтиловый эфир, 1,2-диметоксиэтан, 2-метоксиэтиловый эфир, диоксан и тетрагидрофуран. Предпочтительным растворителем является тетрагидрофуран.The alkynylation reaction is carried out by treating halopyridine (4) with alkine (13)

wherein W and n are as defined above in an acid acceptor, such as di- or trialkylamines, such as diethylamine, dipropylamine, trimethylamine, or tripropylamine, in the presence of bis (triphenylphosphine) palladium / cuprous iodide at a temperature of about 0-75 ^{° C.} A preferred acid acceptor is triethylamine. The preferred temperature is the alkylation temperature is about 50-60 ° ^C. This ether solvent can be used. Such ether solvents are diethyl ether, 1,2-dimethoxyethane, 2-methoxyethyl ether, dioxane and tetrahydrofuran. A preferred solvent is tetrahydrofuran.

The reduction reaction alkilpiridinilpropionata (5) in propanediol (6) is carried out using an alkali borohydride in an ethereal solvent at a reduction temperature in the range of about 0-50 ° ^C. These alkali metal borohydrides are calcium borohydride, lithium borohydride, potassium borohydride and sodium borohydride. Examples of ether solvents are diethyl ether, 1,2-dimethoxyethane, 2-methoxyethyl ether, dioxane and tetrahydrofuran. Preferred is the reduction system of lithium borohydride or calcium borohydride in tetrahydrofuran at a temperature of about 0-25 ^about C.

Hydrolysis of carboxamide (6) into aminodiol (7) can be carried out using standard hydrolysis techniques. For example, carboxamide (6) can be hydrolyzed using an alkali metal hydroxide, for example lithium hydroxide, sodium or potassium, in an aqueous alkanol such as methanol, ethanol or 1- or 2-propanol, at a hydrolysis temperature of about 0-100 ^C. .

 In order to obtain 1-alkylpyridinal-2-amino-1,3-propanediol (9), where W, X and m are defined above, 1-alkynylpyridinyl-2-amino-1,3-propanediol (6) is hydrogenated to give 1- alkynylpyridinyl-2-amido-1,3-propanediol (8), which is converted to 1-alkylpyridinyl-2-amino-1,3-propanediol (9).

Hydrogenation is carried out by treating alkyne (6) with hydrogen at atmospheric pressure up to about 60 psi. inch (413.6 kPa), preferably about 40 psi (275.7 kPa), in the presence of a metal catalyst, for example a platinum, palladium, rhodium or ruthenium catalyst without a support or supported on a substrate of coal or calcium carbonate, this preferred is palladium on charcoal, and in the presence of an alkanol, e.g., methanol, ethanol, or 1- or 2-propanol, preferably ethanol, at a hydrogenation temperature of about 25-50 ^{° C,} preferably at 25 ° ^C.

The conversion of pyridinylamidodiol (8) to pyridinylamidodiol (9), i.e. hydrazinolysis (8) is carried out using hydrazine in free or hydrated form, in an alkanol, e.g., such as methanol, ethanol or 1- or 2-propanol, at a temperature from about 25 C to ^about the reflux temperature of the reaction mixture. Ethanol is the preferred solvent. The temperature of hydrazinolysis is preferably the distillation temperature of the reaction mixture.

Alternatively, the preparation of 1-alkynyl- and 1-alkylpyridinyl-2-amino-1,3-propanediol systems, i.e., systems of formulas (7 and 9), respectively, where W, X and n are defined above, can be achieved by alkynylation of pyridinylcarboxaldehyde (2) where W, X and Y are defined above, in alkynyl pyridinyl carboxaldehyde (10), where W, X and m are defined above, followed by the conversion of pyridinyl carboxaldehyde (10) to pyridinyl propionate (5), where R ₁₁ , R ₁₂ , W, X and m are as defined above, and hydrogenating alkinilpiridina (5) wherein R _11, R _12, W, X and m are as defined above, into a compound (11) wherein R _11, R _12, W, X and m opred Lena above. The alkynylation reaction, conversion and hydrogenation, i.e. transformations 2 to 5 and 11 through 10, carried out by methods basically similar to the corresponding transformations 4 to 5, 2 to 4 and 6 to 8.

Alkyl 1-alkyl pyridinyl propionate (11), where R ₁₁ , R ₁₂ , W, X and m are defined above, can be reduced to 1-alkyl pyridinyl propanediol (8) by a method essentially similar to that used to reduce alkyl pyridinyl propionate (5) into propanediol ( 6).

Obtaining a series of 1-alkynylpyridinyl-2-amino-1,3-propanediol, i.e. a number of compounds represented by formulas 5, 6 and 7 can also be achieved by reducing alkyl pyridinyl propionate (4), where R ₁₁ , R ₁₂ , W, X and Y are defined above, in pyridinyl propanediol (12), and alkynylating the pyridinyl diol thus obtained ( 12) to alkynylpyridinediol (6). As indicated above, amidopropanediol (6) is converted to aminopropanediol (7) by hydrolysis. Similarly, the reduction of 4 to 12 and alkynylation of 12 to 6 are carried out essentially in the same manner as that used to convert 5 to 6 and 4 to 5.

Derivatives of alkynylpyridinyl-2-amino-1,3-diol (7) are obtained from amidopropanediol (6) by acylation (6), where R ₁₂ , W, X and m are defined above, to amidodiacyloxypropane (15) where, R ₁₂ , R ₁₃ , R ₁₄ , W and m are defined above, using, for example, alkanoic anhydride such as acetic anhydride in the presence of triethylamine and 4-dimethylaminopyridine, and dioxinylation of 6 into amidodioxane 14, where R ₁₂ , R ₁₅ , R ₁₆ , W, X and m are defined above using, for example, 2,2-dimethoxypropane and in the presence of para-toluenesulfuric acid. Hydrolysis (15) (see conversion of 6 to 7) gives aminopropanediol (7). Amidodiacyloxypropane (15) is subjected to selective hydrolysis to obtain amidodihydroxypropane 20, for example, using an alkali metal carbonate such as lithium, sodium or potassium carbonate in an alkanol such as methanol, ethanol or 2-propanol. A preferred hydrolysis medium is potassium carbonate in methanol. The hydrolysis process usually proceeds at room temperature. You can also use a temperature increase up to the temperature of distillation of the hydrolysis mixture.

The acyl derivatives of amidopropanediol (12), where R ₁₂ , X and Y are defined above, are obtained by treating 12 with alkanoic acid anhydride under the same conditions as described for the conversion of 6 to 15.

In order to obtain 1-alkenyl-2-amino-1,3-propanediol (17), where W, X and m are as defined above, 1-alkynyl-2-amino-1,3-propanediol (6), where R ₁₂ , W, X and m are defined above, hydrogenated to obtain 1-alkenyl-2-amino-1,3-propanediol (16), where R ₁₂ , W, X and m are defined above, and the configuration of hydrogen atoms in a carbon-carbon double bond is a cis configuration, which in turn is hydrolysed at 17, where W, X and m are also defined above.

, 2-амиино-1,3-пропандиол (9) обрабатывают N-бензилоксикарбонилоксисукцинимидом 20

NO

OCH

в присутствии третичного амина, например триэтиламина в эфирном растворителе, таком, как тетрагидрофуран, приблизительно при комнатной температуре.To obtain N, 0,0-tribenzyloxycarbonyl-2-amino-1,3-propane (18), where R ₁₅ is

, 2-amino-1,3-propanediol (9) is treated with N-benzyloxycarbonyloxy-succinimide 20

NO

Och

in the presence of a tertiary amine, for example triethylamine in an ethereal solvent such as tetrahydrofuran, at about room temperature.

 For the synthesis of 2-amino-1,3-propanediol (19), 1,3-diacyclosi-2-propanylacetamide (13) is hydrolyzed using hydrazine hydrate in the presence of ethanol in accordance with the procedure described for the conversion of 8 to 9.

Typically, the final 1-alkylaryl-2-amino-1,3-propanediols are prepared from 1-alkynylarylcarboxaldehydes (see Reaction Scheme A for the conversion of 10 to 9 in the pyridine series). In the isoxazole series, the final 1-alkylisoxazolyl-2-amino-1,3-propanediols can be obtained, for example, from 5- (1-alkyl) -3-isoxazolecarboxaldehyde (21), where R _{5 is} dodecyl.

CHO
3- Изоксазолкарбоксальдегид (21), где R₅ является додецилом, в свою очередь синтезируют, например, путем конденсации 1-нитротридекана с 0-триметилсилилпропи- нолом в присутствии фенилизоцианата и триэтиламина, а затем фторида тетрабутиламмония, в результате чего получают изоксазолметанол 22.

Cho
3- Isoxazole carboxaldehyde (21), where R ₅ is dodecyl, is in turn synthesized, for example, by condensation of 1-nitrotridecane with 0-trimethylsilylpropynol in the presence of phenylisocyanate and triethylamine and then tetrabutylammonium fluoride, whereby isoxazole methanol 22 is obtained.

CH₂OH где R₅ - додецил, который может быть окислен до 21 с помощью оксалилхлорида:диметилсульфоксида.

CH ₂ OH where R ₅ is dodecyl, which can be oxidized to 21 with oxalyl chloride: dimethyl sulfoxide.

To obtain 2-alkoxycarbonylamino-1,3-propanediol, for example, 1-alkynyl-2-t-butyloxycarbonylamino-1,3-propanediol (6), where R ₁₂ is OC (CH ₃ ) ₃ , 1-alkynyl -2-amino-1,3-propanediol (7) is acylated with di-t-butyl dicarbonate in the presence of a base such as sodium bicarbonate in a halocarbon solvent such as chloroform at an elevated temperature ^(about 60 C).

 To obtain 2-dialkylamino-1,3-propanediol, for example, 1-alkenyl-2-dimethylamino-1,3-propanediol (23), 1-alkenyl-2-amino-1,3-propanediol (17) reductive alkylation with formaldehyde, such as formalin, in the presence of a reducing agent, such as sodium cyanoborohydride in a solvent, such as acetonitrile, at room temperature.

 1-Alkenyl-2-amino-1,3-propanediol, e.g. 1-alkenylpyridinyl-2-amino-1,3-propanediol (17), is prepared by the reduction reaction of 1-alkynylpyridinyl-2-acylamino-1,3-propanediol (6) by 1-alkenyl-2-acylamino-1,3-propanediol 16 (see Reaction Scheme C). Alternatively, 1-alkenyl-2-amino-1,3-propanediol, for example, 1-alkenylthienyl-2-amino-1,3-propanediol (27) can be obtained by condensation of halogeniophenecarboxyaldehyde (25), where X is bromine, with three n-butyl-1-alkenylstannane (24) in the presence of 2,6-di-t-butyl-4-methylphenol and tetrakis (triphenylphosphine) palladium (0) in an aromatic solvent such as toluene at room temperature to give 1 -alkenylthiophenecarboxaldehyde 26 (see Reaction Scheme D), which in turn is converted to 2-amino-1,3-diol (27) and its derivatives by the methods indicated mi in reaction schemes A, B and C.

 The desired tri-n-butyl-1-alkenyl stannate (24) is obtained by reductive condensation of alkyn (28) with tri-n-butyltin hydride in the presence of azobisisobutyronitrile.

 1-alkyl-, 1-alkenyl- and 1-alkynylaryl-2-amino-1,3-propanediols can be used as drugs for the treatment of memory disorders, in particular disorders associated with reduced cholinergic activity, which, for example, has place with Alzheimer's disease. The mild memory impairment activity of the compounds of the present invention was studied using a mouse avoidance test performed in mice to determine the restorative effect of the subject compounds in scopolamine-induced memory disorders associated with decreased levels of brain acetocholine. In this test, three groups of 15 CFW mice (males) were used, namely, the vehicle / vehicle control group, the scopolamine / vehicle group, and the scopolamine / drug group. 30 minutes before training the vehicle / vehicle control group, normal saline was administered subcutaneously, and scopolamine (3.0 mg / kg administered as scopolamine hydrohydride) was administered subcutaneously to the scopolamine / vehicle and scopolamine / drug groups. Distilled water was administered 5 minutes prior to the start of training for the control vehicle / vehicle and the scopolamine / vehicle group, and the test compound was administered in distilled water to the scopolamine / drug group.

 The device for training / testing contained a plexiglass chamber approximately 48 cm long, 30 cm high, which has a conical shape, pointed downward (with a width of 26 cm in the upper part and up to 3 cm in the lower part). Inside, this chamber is divided by a vertical partition into two equal compartments, a light compartment (illuminated by a 25 W mirror lamp suspended 30 cm above the floor) and a dark compartment (covered). In the lower part of the partition there is an opening 2.5 cm wide and 6 cm high and a trap door, which can be lowered to prevent the animal from entering the neighboring compartment. The device for causing shock in small animals was connected to two metal plates that could move along the entire length of the device, and a photocell increased in the dark compartment at a distance of 7.5 cm from the vertical partition and 2 cm from the floor. The behavior of animals was controlled using a minicomputer 11/34 with a program-controlled processor for data processing (PDP).

 At the end of the pre-training period, the animals were placed in a bright compartment directly under a fixed light source, so that the animals were facing the muzzle from the door leading to the dark compartment. Then the device was closed and the system was powered. If the mice passed through the partition into the dark compartment and interrupted the beam of the photocell for 180 s, then the door went down, blocking the exit to the bright compartment, and the mice were exposed to an electric current of 0.4 mA for 3 s. After this, the animals were immediately removed from the dark compartment and placed in their cages. If the animals could not interrupt the beam of the photocell for 180 s, then these animals were eliminated from the tests. Latency in seconds was recorded for each mouse.

 After 24 hours, the animals were again tested in the same device, except that the mice were not injected and were not shocked. For each mouse, latent time in seconds was recorded during the daytime test, after which the animals were removed.

 Specialists are well aware that in one type of passive avoidance behavior during testing there is a high degree of variability (depending on the time of year, conditions of detention and care). In order to take into account the indicated factor for each test, individual neglected values (CO) were determined that compensate for the indicated variability. In addition, it was found that 5-7% of mice in the scopolamine / vehicle control groups were insensitive to a dose of scopolamine of 3 mg / kg. Thus, CO values were determined as the second highest latent period in the control group to more accurately reflect 1/15 of the expected control responses in each test group. Experiments with a number of standards, which were repeated under different environmental conditions, allowed us to develop the following criteria: for the test under consideration, the CO-values should be less than 120 s, the control group "filler / filler" should have at least 5/15 animals with latent periods exceeding CO. To combine the activity in question, the scopolamine / compound group must have at least 3/15 with latent periods in excess of CO.

 The results of the avoidance test were expressed as the number of animals per group% in which scopolamine-induced memory disorder is blocked, measured by increasing the latent period. Activity to restore memory disorders of characteristic compounds of the present compounds are presented in table 1.

 The restoration of scopolamine-induced memory disorder was achieved with the introduction of 1-alkyl-, 1-alkenyl- and 1-alkynylaryl-2-amino-1,3-propanediol and related compounds into the body with this disorder orally, parenterally or intravenously at a dose of 0, 01 to 100 mg / kg of body per day. Especially effective is the amount of 25 mg / kg of body per day. However, it is obvious that for each specific case, a certain mode can be established in accordance with the individual characteristics of the organism and the method of administration of the specified compound. It goes without saying that the above doses are illustrative and in no way limit the scope of the present invention.

 1-Alkyl-, 1-alkenyl- and 1-alkynaryl-2-amino-1,3-propanediols can also be used as anti-inflammatory drugs due to their ability to reduce inflammatory processes in mammals. The anti-inflammatory activity of the compounds was tested using a TPA-induced ear swelling test and an arachidonic acid test for ear swelling.

 In this assay for TPA-induced ear edema, TPA (12-0-tetradecanoylphorbol-13-acetate) was dissolved in a mixture of propylene glycol and ethanol (30:70) and the solution was applied to the right ear of a group of 6 mice (females) Swiss Webster mice which, 1 week before their use, were placed together in a cage under standard conditions with food and water as desired, while the treatment was carried out with a volume of 20 μl so that a total of 10 μg TPA fell on the inner and outer surfaces of the ear. The test compound was dissolved in the vehicle and applied to the right ear (inner and outer surfaces) in a volume of 20 μl so that a total of 10 μg of compound was present in the ear. After about 5 hours, the animals were killed and a 4 mm diameter insert was removed from each ear and weighed, after which the difference between the weights of the right and left ears for each animal was determined. The anti-inflammatory activity of the test compound was expressed as the average change in percentage of the weight of the ear liner of the treated animals compared to the average change in weight of the liner of the control animals. The results of determining the anti-inflammatory activity of the characteristic compounds of the present invention are presented in table.2.

 In the arachidonic acid induced ear swelling assay, the test compound was dissolved in a mixture of propylene glycol and ethanol (30:70) and applied to both ears of a group of 6 Swiss Webster mice (females) that were kept together 1 week before use. in a cage under standard conditions with food and water as desired, while treatment was carried out with a volume of 20 μl so that a total of 1.0 mg of the test compound fell on each ear (inner and outer surfaces). In the control group mice, each ear was treated with the same volume of vehicle (20 μl). After 30 min, arachidonic acid in an amount of 4 mg / ear was applied to the right ear of each group, and a filler in an amount of 20 μl / ear was applied to the left ear of each mouse in each group. After another 1 h, the animals were euthanized and a 4 mm diameter insert was removed from each ear and weighed. For each animal, the difference between the weights of the right and left ear liners was determined. Anti-inflammatory activity was defined as the average percentage change in the weight of the earmold of the treated animals relative to the average percentage change in the weight of the earmold of the control group. The anti-inflammatory activity of the characteristic compounds of the present invention in accordance with the analysis presented in table 3.

 Mitigation of the inflammatory process is achieved by the administration of 1-alkyl-, 1-alkenyl- and 1-acynylaryl-2-amino-1,3-propanediols externally, for example, by ophthalmic administration as an effective dose for external use from 0.001 to 100 mg / kg body per day. A particularly effective amount is a dose of about 25 mg / kg body per day. However, it is obvious that for each individual individual, a specialist may establish a specific application regimen depending on the state of the organism and the route of administration. Therefore, the above doses are illustrative and in no way limit the scope of the present invention.

 1-Alkyl-, 1-alkenyl- or 1-alkynyl-2-aminopropanediols of the present invention can be used as inhibitors of the growth of tumor or malignant cells due to their peculiarity to reduce cell proliferation, as can be shown by analysis on protein kinase C.

Protein kinase C extract prepared from Wistar rat brain (male) weighing 180-200 g and was purified by V.Kikkawa et al., Ibid 636. The purified extract was stored at -80 ^{° C} and aliquots used in the assay for protein kinase C, which was carried out in accordance with a modification of the method of RM BeII et al., ibid 354.

For the analysis used duplicated aliquots of duplicated samples. Each assay involves basal or non-activated protein kinase C, phosphatidylserine / diacylglycerol-activated protein kinase C, and test samples. Protein kinase extract (1-5 μg protein; 10 μl) was added to each tube containing a sample of inactivated ice-cold protein kinase; 8 μl solution of N-2-hydroxyethylpiperazine-N'-2-ethylsulfonic acid (500 mM); magnesium chloride (40 mmol); ethylene diaminotetraacetic acid (10 mM); dithiothreitol (20 mM; 8 μl) histone type III (12 μg; 8 μl) and calcium chloride (11 mm; 8 μl). Phosphatidine-serine / diacylglycerol (4 μg; 8 μl) was added to each tube with an ice-cold activated protein kinase sample. Thereafter, the test compound (10 ^-4 -10 ^-12 M in 4 μl of dimethyl sulfoxide) was added to test tubes with ice-cooled samples. Then the volume of all test tubes was brought to 72 μl with distilled water (18 μl for activated samples, 26 μl for inactive samples without 8 μl phosphatidylserine / diacylglycerol). The test tubes were heated to 25 ^° C and 8 μl of a mixture of adenosine 5 - triphosphate (100 μM) and ³² P-adenosine triphosphate (1-2x10 ⁵ counts per 1 min) were added to each tube to obtain a final volume of 80 μl per tube. After 2 minutes, the incorporation of phosphorus into histone type III was completed by applying the reaction mixture to phosphocellulose paper. The spots applied to the paper were cut out and the radioactivity of each spot (the number of counts per 1 min) was determined in a scintillation counter. Protein kinase C inhibition activity, i.e. the percent inhibition of the incorporation of ³² phosphorus from ³² P-adenosine triphosphate into histone type III was calculated as follows:
test radioactivity
sample count / min

x 100
radioactivity of the activated sample from / min - radioactivity of the inactive sample from / min
The protein kinase C inhibition activity of the characteristic compounds of the present invention, calculated as the concentration of the test compound, inducing 50% inhibition of phosphorus uptake (IC ₅₀ ), is presented in Table 4.

 Inhibition of protein kinase is achieved by administering to the body requiring such treatment 1-alkyl-, 1-alkenyl- and 1-alkynaryl-2-amino-1,3-propanediols of the present invention or related compounds orally, parenterally, intravenously or topically in an effective amount from 0.001 or 0.01 to 100 mg / kg of body per day. A particularly effective amount is a dose of 25 mg / kg body per day. However, it should be borne in mind that for each organism, a specific dosage regimen can be established depending on the condition of the individual and the method of administration of the drug. Therefore, it is obvious that the above doses are illustrated and in no way should limit the scope of the present invention.

The 1-alkyl-, 1-alkenyl- and 1-alkynaryl-2-amino-1,3-propanediols of the present invention can also be used as antifungal and antibacterial agents due to their ability to inhibit bacterial and fungal growth in mammals. Antibacterial and antifungal activity was illustrated using standard analysis of antibacterial activity. An aerobic bacterial susceptibility assay was performed using a Mueller Hinton agar dilution test. The cups were inoculated using a multi-point inoculator, into which 5 x 10 ⁴ CFU / spot of stationary, freshly bred cultures of the considered strains were introduced. For minimum inhibitory concentration MIC took the lowest concentration at which no visible growth is observed after 24 hours at 37 ° ^C.

Anaerobic analysis, i.e. sensitivity analysis to obligate gram-positive and gram-negative anaerobes was performed using dilutions in Wilkins-Chalgren agar. Night cultures of the respective test strains diluted 1:10 in fresh thioglycolate medium were used as inoculum. After the cups were incubated for 48 hours at ³⁷ ° C Anaerobic determined MIC of antibiotics.

 The antibacterial activity of the characteristic compounds of the present invention, as defined in the above analysis, is presented in tables 5 and 6.

 The analysis of antifungal activity was carried out using the microtiter technique (96-well U-shaped plate), in which the test compound (10 mg) was dissolved in an appropriate solvent (10 ml of distilled water or 1 ml of organic solvent + 9 ml of distilled water).

A microtiter tablet was prepared as follows. Each well was filled (2 rows / strain) with 50 μl of neopeptonextrose broth (12-channel pipette). In addition, 1 row / strain was coated with 50 μl of a mixture of yeast and a nitrogen base per well for yeast and molds. Then, 50 μl of a solution of the compound was added to each well of the first row, mixed and diluted another 50 μl, respectively, in a 1: 2 ratio. After that, all wells were inoculated with 150 μl of a titrated suspension of yeast organisms: 1 x 10 ³ organism / ml suspension; dermatomycetes and molds: 1.6 x 10 ⁵ organism / ml suspension; the total volume was 200 μl per well.

Control samples were also used: by growth (inoculated, without drug administration), by solvent (inoculated, without drug administration, containing a solvent instead of the drug in the appropriate rows) and negative control samples (not inoculated), without drug administration) . Incubation was carried out for 5 days at 30 ^{° C,} followed by photometric evaluation. The measurements were checked visually macroscopically and microscopically and, if necessary, carried out the appropriate correction.

Criterion for evaluating antifungal activity:
a) photometric measurements (matrix method);
b) growth (macroscopic assessment);
c) growth (microscopic evaluation - inverse optical microscope, enlarged. 64x).

 The antifungal activity of the characteristic compounds of the present invention, determined as a result of microtiter analysis, is presented in Table 7.

 Inhibition of bacterial and fungal growth can be achieved by administering 1-alkyl-, 1-alkenyl- and 1-alkynylaryl-2-amino-1,3-propanediols or related compounds of the present invention in the body, requiring appropriate treatment, oral, parenteral, intravenous or topically, for example, by ophthalmic administration in an amount of from 0.01 to 100 mg / kg body per day. A dose of 25 mg / kg of body per day is especially effective. However, it should be noted that for each individual organism, a specific regimen for the use of the drug may be established depending on the state of the organism and the method of administration of the above compound. Therefore, it is obvious that the above doses are illustrative and in no way limit the scope of the present invention.

The compounds of the present invention are:
a) erythro-2-amino-1- (5-decyl-2-furyl) -1,3-dihydroxypropane;
b) erythro-2-amino-1- (5-decyl-3-isothiazolyl) -1,3-dihydroxypropane;
c) threo-2-amino-1- [5-decyl-3- (2-oxopyrrolyl)] -1,3-dihydroxypropane;
d) erythro-2-amino-1- [6-decyl-2- (4-methylpyridinyl)] -1,3-dihydroxypropane;
e) threo-2-amino-1- [6-decyl-2- (4-methoxypyridinyl)] -1,3-dihydroxypropane;
f) erythro-2-amino-1- [6-decyl-2- (5-chloropyridinyl)] -1,3-dihydroxypropane;
g) threo-2-amino-1- [6-decyl-2- (4-trifluoromethylpyridinyl)] -1,3-dihydroxypropane;
h) erythro-2-amino-1- [6- (5-phenylpentyl-2-pyridinyl)] -1,3-dihydroxypropane;
i) erythro-2-amino-1- (2-decyl-4-thiazolyl) -1,3-hydroxypropane;
j) erythro-2-amino-1- (2-decyl-4-oxazolyl) -1,3-dihydroxypropane;
k) erythro-2-methylamino-1- (5-decyl-2-thienyl) -1,3-dihydroxypropane;
l) erythro-2-dimethylamino-1- (3-decyl) phenyl-1,3-dihydroxypropane;
m) erythro-2- (1,1-dimethoxy) carbonyl-amino-1- (2-dodecynyl-6-pyridinyl) -1,3-dihydroxypropane;
n) erythro-2-amino-1- [3- (1-decenyl) phenyl] -1,3-dihydroxypropane;
o) ethyl erythro-2-methoxycarbonylamino-3- (2-dodecyl-6-pyridinyl) -3-hydroxy-propionate;
p) erythro-2-amino-1- [3- (1-decynyl) phenyl] -1,3-dihydroxypropane;
q) erythro-2-amino-1- [3- (1-undecynyl) phenyl] -1,3-dihydroxypropane;
r) erythro-2-amino-1- (4- (1-nonyl) -2-thienyl] -1,3-dihydroxypropane;
s) erythro-2-amino-1- [4- (1-dodecynyl) -2-thienyl] -1,3-dihydroxypropane;
t) erythro-2-amino-1- [4- (1-decyl) -2-thienyl] -1,3-dihydroxypropane;
u) erythro-2-amino-1- (5-nonyl-2-thienyl) -1,3-dihydroxypropane;
v) erythro-2-amino-1- (3-dodecyl-5-isoxazolyl) -1,3-dihydroxypropane;
w) erythro-2-amino-1- (3-decyl-5-isoxazolyl) -1,3-dihydroxypropane;
x) erythro-2-amino-1- [6- (1-dodecynyl) -2-pyridinyl] -1,3-dihydroxypropane;
y) erythro-2-amino-1- [3- (6-phenyl-1-hexynyl) phenyl] -1,3-dihydroxypropane;
z) erythro-2-amino-1- [5- (6-phenylhexyl) -2-thienyl] -1,3-dihydroxypropane.

 Effective amounts of the present invention can be administered by topical administration in the form of sterile solutions, suspensions, ointments, creams or suspensions. The 1-alkyl-, 1-alkenyl- and 1-alkynaryl-2-amino-1,3-propanediols of the present invention, which are themselves effective, can be administered as their pharmaceutically acceptable acid or base addition salts for greater stability convenience, crystallization, increased solubility, etc. Preferred pharmaceutically acceptable acid addition salts of the compounds of the present invention are salts of mineral acids, for example hydrochloric acid, sulfuric acid, etc., salts of monobasic carboxylic acids, for example acetic acid, propionic acid and the like, salts of dibasic carboxylic acids, for example maleic , fumaric and other acids, and salts of tribasic carboxylic acids, for example, carboxylic succinic acid, citric acid, etc. Preferred pharmaceutically acceptable base addition salts with The compounds of the present invention are alkali metal salts, for example sodium or potassium; alkaline earth metal salts, for example calcium or magnesium; or complex salts, such as ammonium or substituted ammonium salts, for example mono-, di- or trialkylammonium salts or mono-, di- or trihydroxyalkylammonium salts.

 For topical use, the active compounds of the present invention can be incorporated into solutions, suspensions, creams, gels, aerosols or ointments. These preparations may contain at least 0.1% active compound, however, the amount of said active compound may vary from 0.05 to about 20% by weight. The amount of active compound in these compositions should be such that it corresponds to the desired dose. Preferred preparations for external use contain from 0.1 to 10% of the active compound.

 Compositions for external use may also include the following components: water, fixed oils, polyethylene, glycols, glycerin, oil, stearic acid, beeswax, other synthetic solvents and mixtures thereof; antibacterial agents, such as benzyl alcohol or methyl paraben; antioxidants such as α-tocopherol acetate; chelating agents such as ethylenediaminetetraacetic acid; buffers, such as acetates, citrates or phosphates; emulsifying agents, such as polyoxyethylene monooleate, as well as dyes and adjuvants, such as iron oxide (3) or talc. Preparations for external use may be contained in tubes, bottles or jars made of metal, glass or plastic.

 The active compounds of the present invention can also be administered orally, for example, in combination with an inert diluent or food excipient. They can be enclosed in gelatin capsules or compressed into tablets. For oral administration, the above compounds can be used in combination with inert excipients in the form of unit dosage forms such as tablets, troches, capsules, elixirs, suspensions, syrups, cachets, chewing gums, and the like. These preparations may contain at least 0.5% of the active compound, however, its amount may vary, depending on its particular type, from about 4 to about 75% by weight of a single dose. The amount of the compound of the present invention in such compositions should correspond to the desired dose. Preferred compositions and preparations of the present invention are those in which a single dose for oral administration contains 1.0-300 mg of the active compound.

 Tablets, pills, lozenges, capsules, etc. may contain the following ingredients: a binder, for example microcrystalline cellulose, tragacanth or gelatin; an inert filler such as starch or lactose; a disintegrating agent such as alginic acid, primogel, corn starch and the like; a sizing agent, such as magnesium stearate or steroids; a glidant such as colloidal silicon dioxide; a sweetener, for example sucrose or saccharin, or a flavoring agent, such as peppermint, methyl salicylate, or an orange flavor. If the unit dosage form is a capsule, then, in addition to the above substances, it may also contain a liquid carrier, such as a fatty oil. Other dosage forms may contain other substances intended to modify the appearance of the dosage form, for example, such as coatings. Tablets or dragees may be coated with sugar, shellac or other enteric coating. The syrup may contain, in addition to the active compounds, a sweetener, for example sucrose, as well as certain preservatives, colorants and flavorings. All substances used in the manufacture of the various compositions described above must be pharmaceutically pure and non-toxic.

 For parenteral administration, the active compounds of the present invention may be included in solutions or suspensions. These preparations should contain at least 0.1% of the active compound, however, its amount may vary from 0.5 to about 50 wt.%. The amount of active compound in such compositions should correspond to the required dose. Preferred compositions and preparations of the present invention for parenteral administration are compositions in a unit dosage form containing from 0.5 to 100 mg of the active compound.

 Oral solutions and suspensions may also contain the following components: a sterile diluent, such as water for injection, saline, fixed oil, polyethylene glycol, glycerin, propylene glycol or other synthetic solvents; antibacterial agents, such as benzyl alcohol or methyl paraben; antioxidants such as ascorbic acid or sodium bisulfate; gelling agents, such as ethylenediaminetetraacetic acid; buffers, such as acetates; citrates or phosphates; and tonicity agents, such as sodium chloride or dextrose. A preparation for parenteral administration may be in the form of ampoules, and may also be contained in disposable syringes or in multiple dose vials made of glass or plastic.

 PRI me R 1. 6- (1-Dodecynyl) -2-pyridinecarboxaldehyde.

To a solution of 6-bromo-2-pyridinecarboxaldehyde (3.0 g) in tetrahydrofuran (10 ml) was added sequentially bis (triphenylphosphine) palladium chloride (11) (0.178 g), copper iodide (1) (0.024 g) 1-dodecin ( 3.25 ml) and triethylamine (2.1 ml). The solution was stirred overnight at 40 ^C. The reaction mixture was cooled to room temperature, charged again chloride bis (triphenylphosphine) palladium (11) (0.024 g), copper iodide (1) (0.024 g) and triethylamine (2.12 ml ) and 1-dodecynyl (3.25 ml) and tetrahydrofuran (5.0 ml) and heated ^at 40 ° C for 5 hours. The reaction mixture was cooled again and again charged as described above, and heated at 40 ^about 24 hours. The cooled mixture was concentrated, diluted with ethyl acetate (100 ml), washed with water and a saturated solution of sodium chloride, dried was taken up with anhydrous magnesium sulfate, filtered and the filtrate was concentrated. The residue was dissolved in ethyl acetate (100 ml) and filtered. The filtrate was combined with a product from a similar reaction batch of 1.43 g of carboxaldehyde and the corresponding proportional amounts of catalyst, 1-dodecin and solvent. The filtrate was concentrated. The residue was purified by flash chromatography using a 1.5% mixture of ethyl acetate and hexane as eluents, followed by a 1% mixture of acetate and hexane. Suitable fractions were collected and concentrated to give 2.24 g (29%) of the product as an oily substance.

 Found,%: C 79.54; H, 9.29; N, 4.98.

C ₁₈ H ₂₅ NO
Calculated,%: C 79.66; H 9.28; N, 5.16.

 Example 2. Erythro-N- {1- [6- (1-decynyl) -2-pyridinyl] -1,3-dihydroxy-2-propanyl} acetamide.

Ethyl erythro-2-acetamido-3- [6- (1-decinyl) -2-pyridinyl] -3-hydroxypropionate (5.71 g) in dry tetrahydrofuran (75 ml) was slowly added to 2.0 M borohydride lithium and tetrahydrofuran (7.6 ml) at ⁰ ° C under a nitrogen atmosphere, and the mixture was stirred overnight at room temperature. The reaction mixture was cooled and a mixture of methanol and water (1: 1), (50 ml) was slowly added, followed by the addition of acetic acid (0.5 ml) until the pH was 6.5, after which the reaction mixture was concentrated. and the residue was made azeotropic with methanol (4 x 40 ml). The residue was suspended in a 7.5% sodium bicarbonate solution (15 ml, pH 8.5), extracted into 3: 1-trichloromethane: isopropanol and concentrated. The appropriate fractions were collected and concentrated. The residue was purified by flash chromatography on silica gel, eluting with a mixture of ethyl acetate and methanol (49: 1). The appropriate fractions were collected and concentrated, whereby 4.74 g (93%) of the product were obtained, mp. 85-87 ^about S.

 Found,%: C 69.44; H, 8.84; N, 8.07.

C ₂₀ N ₃₀ N ₂ O ₃
Calculated,%: C 69.33; H 8.73; N, 8.09.

 Example 3. Erythro-N- {1- [6- (1-decynyl) -2-pyridinyl] -1,3-diacetyloxy-2-propanyl} acetamide.

 N- {1- [6- (1-Decynyl) -2-pyridinyl] -1,3-dihydroxy-2-propanyl} acetamide (4.35 g), acetic acid (7.45 ml), triethylamine (16 ml ) and 4-dimethylaminopyridine (0.24 g) in dry tetrahydrofuran (80 ml) was stirred at room temperature for 3 days. The reaction mixture was evaporated and the residue was heated with methanol for 20 minutes, after which it was again evaporated and the residue was made azeotropic with toluene. The residue was dissolved in trichloromethane, after which a 7.5% sodium bicarbonate solution was added until the pH was 8.5. The mixture was extracted with trichloromethane, dried over anhydrous magnesium sulfate, filtered and the filtrate was concentrated. The residue was combined with the residue (1.0 g) from another reaction (0.829 g of acetamide) and purified by flash chromatography on silica gel, eluting with a mixture of hexane and ethyl acetate (1: 1). The appropriate fractions were collected, concentrated to give 1.61 g (25%) of the product.

 Found,%: C 68.65; H, 8.04; N, 6.36.

C ₂₄ H ₃₄ N ₂ O ₅
Calculated,%: C 66.95; H 7.96; N, 6.51.

 Example 4. Treo-N- {1- [6- (1-decynyl) -2-pyridinyl] -1,3-diacetyloxy-2-propanyl} acetamide.

N- {1- [6- (1-Decinyl) -2-pyridinyl] -1,3-dihydroxy-2-propanyl} acetamide (4.35 g), acetic acid (7.45 ml), triethylamine (16 ml ) and 4-dimethylaminopyridine (0.24 g) in anhydrous tetrahydrofuran (80 ml) were stirred at room temperature for 3 days. The reaction mixture was evaporated, and the residue was heated with methanol for 20 minutes, after which it was again evaporated and made azeotropic using toluene. The residue was dissolved in trichloromethane and a 7.5% sodium bicarbonate solution was added to adjust the pH to 8.5. The mixture was extracted with trichloromethane, dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was combined with 10 g of the residue from another reaction (0.929 g of acetamide) and purified by flash chromatography on silica gel, eluting with a mixture of hexane and ethyl acetate (1: 1), whereby 1.02 g (15.9%) of the product was obtained , mp 59-61 ^about S.

 Found,%: C 66.21; H 7.83; N, 5.92.

C ₂₄ H ₃₄ N ₂ O ₅
Calculated,%: C 66.95; H 7.96; N, 6.51.

PRI me R 5. Ethyl erythro-2-acetamido-3- [6- (1-decynyl) -2-pyridinyl] -3-hydroxy-propionate
Erythro: threo-mixture (2: 1) ethyl 2-acetamido-3- (6-bromo-2-pyridinyl) -3-hydroxypropionate (10.0 g), 1-decene (5.01 g), bis (triphenylphosphine) palladium chloride (0.42 g) and copper iodide (0.06 g) in triethylamine (50 ml) was heated for 2.5 hours at 50-60 ^{° C} under a nitrogen atmosphere and then allowed to stand overnight at room temperature. Then the reaction mixture was evaporated, water was added and extracted with ethyl acetate. The organic extract was purified by flash chromatography on silica gel, eluting with a mixture of hexane and ethyl acetate (1: 1), and the appropriate fractions were collected. The resulting fractions were evaporated. Recrystallization from ethyl acetate gave 7.8 g (66%) of the product, mp. 97-99 ^about S.

 Found,%: C 68.23; H, 8.28; N, 7.22.

C ₂₂ H ₃₂ N ₂ O ₄
Calculated,%: C 68.01; H, 8.30; N, 7.21.

 Example 6. Ethyl-threo-2-acetamido-3- [6- (1-decinyl-2-pyridinyl] -3-hydroxypropionate.

A mixture of ethyl 2-acetamido-3- (6-bromo-2-airidinyl) -3-hydroxypropionate (17.3 g, 97% erythro), 1-decine (8.67 g), palladium bis (triphenylphosphine) chloride ( 0.73 g), copper iodide (0.10 g) and triethylamine (13.2 g) in tetrahydrofuran (90 ml) was heated overnight at 50-55 ^{° C} under a nitrogen atmosphere. The reaction mixture was evaporated, water was added and the resulting mixture was extracted with ethyl acetate and concentrated. The residue was purified by flash chromatography on silica gel, eluting with a mixture of hexane and ethyl acetate (1: 1). The appropriate fractions were collected and evaporated. After recrystallization of the residue from a mixture of hexane and ethyl acetate (1: 2), 14.7 g of a mixture of erythro: threo (19: 1) compounds were obtained, and from a mother liquor 4.66 g of a mixture of erythro: threo (8: 3) compounds. After flash chromatography, 2.63 g of a threo-enriched product on silica gel, eluting with a mixture of hexane and ethyl acetate (1: 1), 0.39 g (3.4%) of the product are obtained, m.p. 97-99.5 ^about S.

 Found,%: C 67.89; H, 8.26; N, 7.10.

C ₂₂ H ₃₂ N ₂ O ₄
Calculated,%: C 68.01; H 8.30; N, 7.21.

 Example 7. Erythro-N- {4- [6- (1-decynyl) -2-pyridinyl] -2,2-dimethyl-1,3-dioxan-5-yl} acetamide.

 N- {1- [6- (1-decynyl) -2-pyridinyl] -1,3-dihydroxy-2-propanyl} acetamide (6: 1 g of a mixture of erythro: threo 3: 1), n-toluenesulfonic acid (3 7 g) and 2,2-dimethoxypropane (43 ml) in dichloromethane (115 ml) were stirred overnight at room temperature under a nitrogen atmosphere. Then the reaction mixture was extracted with 0.5 M sodium bicarbonate solution and water, dried over anhydrous magnesium sulfate, filtered and the filtrate was evaporated. The residue was chromatographed on silica gel, eluting with a mixture of hexane and ethyl acetate (2: 1), and 2.4 g (35%) of the product was obtained as an oil.

 Found,%: C 71.14; H, 9.12; N, 7.13.

C ₂₃ H ₃₄ N ₂ O ₃
Calculated,%: C 71.47; H, 8.87; N, 7.25.

 Example 8. Treo-N- {4- [6- (1-decynyl) -2-pyridinyl] -2,2-dimethyl-1,3-dioxan-5-yl} acetamide.

 N- {1- [6- (1-decynyl) -2-pyridinyl] -1,3-dihydroxy-2-propanyl} acetamide (6.1 g, 3: 1 mixture of erythro-threo), p-toluenesulfonic acid ( 3.7 g) and 2,2-dimethoxypropane (43 ml) in dichloromethane (115 ml) were stirred overnight at room temperature and under nitrogen. Then the reaction mixture was washed with 0.5 M sodium bicarbonate solution and water, dried with anhydrous magnesium sulfate, filtered, and the filtrate was evaporated. The residue was chromatographed twice on silica gel, eluting with a mixture of hexane and ethyl acetate in a gradient (2: 1 - 1: 1), and 0.76 g (11%) of the product was obtained as an oily substance.

 Found,%: C 71.15; H, 8.91; N, 7.06.

C ₂₃ H ₃₄ N ₂ O ₃
Calculated,%: C 71.47; H, 8.87; N, 7.25.

 PRI me R 9. Ethyl-erythro-2-acetamido-3- [6- (1-dodecynyl) -2-pyridinyl] -3-hydroxypropionate.

A solution of 6- (1-dodecynyl) -2-pyridinecarboxaldehyde (5.51 g), acetamidomalonic acid monoethyl ester (3.78 g) and triethylamine (2.8 ml) in dry tetrahydrofuran (30 ml) was stirred at room temperature and under nitrogen overnight. Then the reaction mixture was evaporated, and the residue was purified on a silica gel column, eluting with a mixture of hexane and ethyl acetate (1: 1), whereby 7.46 g (89.6%) of the product (10: 1-erythro: threo mixture) was obtained . The product was combined with 7.40 g from another reaction batch on the same scale, and the resulting combined product was recrystallized from a mixture of ethyl acetate and hexane (2: 1), whereby 9.62 g (57.7%) of analytically pure product was obtained, so pl. 86-87.5 ^about S.

Found,%: C 69.40; H, 8.72; N, 6.68;
C ₂₄ H ₃₆ N ₂ O ₄
Calculated,%: C 69.20; H 8.71; N, 6.72.

 PRI me R 10. Ethyl erythro-2-acetamido-3- [6- (1-hexynyl) -2-pyridinyl-3-] hydroxypropionate.

Erythro-threo (11: 1) - a mixture of ethyl 2-acetamido-3- (6-bromo-2-pyridinyl) -3-hydroxypropionate (24.9 g), 1-hexine (7.39 g), triethylamine (19.0 g) of bis (triphenylphosphine) palladium (1.05 g) and copper iodide (0.14 g) in anhydrous tetrahydrofuran (100 ml) was heated for 6 hours at 55 ^{° C} under a nitrogen atmosphere. Then at room temperature another 6.2 g of 1-hexine, 7.6 g of triethylamine, 0.53 g of bis (triphenylphosphine) palladium chloride and 0.07 g of copper iodide were added, and the resulting reaction mixture was heated for another 5.5 hours. After this mixture was evaporated, water was added and extracted with ethyl acetate. The extract was chromatographed on silica gel, eluting with a mixture of hexane and ethyl acetate (1: 1). The appropriate fractions were collected and evaporated. Recrystallization of the residue from a mixture of hexane and ethyl acetate (1: 1) afforded 3.8 g (15%) of product, mp pl.87-88 ^° C.

 Found,%: C 65.19; H, 7.31; N, 8.37.

C ₁₈ H ₂₄ N ₂ O ₄
Calculated,%: C 65.04; H 7.28; N, 8.43.

 PRI me R 11. Erythro-N- {1,3-diacetyloxy-1- [6- (1-hexynyl) -2-pyridinyl] -pro-panyl} acetamide.

To ethylerythro-2-acetamido-3- [6- (1-hexynyl) -2-pyridinyl] 3-hydroxypropionate (16.0 g) in anhydrous tetrahydrofuran (140 ml) was added 2.0 M lithium borohydride / tetrahydrofuran (24 ml ) at ⁰ ° C with stirring under a nitrogen atmosphere. Upon completion of the addition, the mixture was left at room temperature and stirred overnight. The mixture was then cooled and a mixture of water and ethanol (1: 1) was slowly added, followed by 2.8 ml of acetic acid) in order to bring the pH to 6.8. The resulting mixture was stirred for 1 h and evaporated. The residue was azeotroped several times with methanol. Then, a 7.5% sodium bicarbonate solution was added to the residue to obtain a pH of 8.5, and the resulting mixture was extracted with a mixture of trichloromethane and isopropanol (3: 1) and concentrated. The residue was flash chromatographed, eluting with 1% methanol-ethyl acetate, to give 13.2 g (94%) of erythro-N- {1- [6-hexyl) -2-pyridinyl] -1,3-dihydroxy-2-propanyl } acetamide. Erythro-N- {1- [6- (1-hexynyl) -2-pyridinyl] -1,3-dihydroxy-2-propanyl} acetamide (10.3 g), acetic anhydride (21.8 g), triethylamine (32.4 g) and 4-dimethylaminopyridine (0.44 g) in tetrahydrofuran (150 ml) were stirred at room temperature overnight. The reaction mixture was evaporated and to the residue was added methanol and the resulting solution was heated for 15 minutes at 50 ^C. The mixture was evaporated, the residue dissolved in chloroform and added with 7.5% strength sodium bicarbonate solution until pH 8 and the mixture was extracted with chloroform . The extract was dried over anhydrous magnesium sulfate, filtered and the filtrate was concentrated. The residue was flash chromatographed, eluting with a mixture of hexane and ethyl acetate (1: 1), and 7.3 g (55%) of the product were obtained, mp. 97-99 ^about S.

 Found,%: C 64.17; H, 7.00; N, 7.44.

C ₂₀ H ₂₆ N ₂ O ₅
Calculated,%: C 64.16; H 7.00; N, 7.48.

 Example 12. Erythro-N- {1- [6- (1-hexynyl) -2-pyridinyl] -1,3-dihydroxy-2-propanyl} acetamide.

Erythro-N- {1,3-diacetyloxy-1- [6- (1-hexyninyl) -2-pyridinyl] -2-propanyl} acetamide (6.7 g) and potassium carbonate (3.3 g) methanol (100 ml) was stirred for 40 minutes. The precipitate was collected and the filtrate was evaporated. A 7.5% sodium bicarbonate solution was added to adjust the pH to 8.5, and the resulting mixture was extracted with a mixture of trichloromethane and 2-propanol (3: 1), dried over anhydrous magnesium sulfate, and the filtrate was evaporated. After recrystallization of the residue from a mixture of hexane and ethyl acetate (1: 1), 4.6 g (88%) of the product are obtained, mp. 75-77 ^about S.

 Found,%: C 65.99; H 7.55; N, 9.65.

C ₁₆ H ₂₂ N ₂ O ₅
Calculated,%: C 66.19; H 7.64; N, 9.65.

 PRI me R 13. Ethyl-erythro-2-acetamido-3-hydroxy-3- [6- (1-octinyl) -2-pyridinyl] propionate.

A mixture of (erythro: threo 11: 1) ethyl 2-acetamido-3- (6-bromo-2-pyridinyl) -3-hydroxypropionate (24.9 g), 1-octin (9.9 g), triethylamine ( 19.0 g) of bis (triphenylphosphine) palladium (1.05 g) and copper iodide (0.14 g) in anhydrous tetrahydrofuran (100 ml) was heated for 6 hours at 55 ^{° C} under a nitrogen atmosphere. Then, another 4.1 g of 1-octin, 3.8 g of triethylamine, 0.53 g of bis (triphenylphosphine) palladium chloride and 0.07 g of copper iodide were added at room temperature, and the reaction mixture was heated for another 4 hours. After that, the mixture was evaporated water was added and extracted with ethyl acetate. The solution was flash chromatographed on silica gel, eluting with hexane and ethyl acetate (1: 1). The fractions enriched in the erythro isomer were evaporated, and the residue was recrystallized from a mixture of isopropanol and water (1: 1), whereby 3.2 g (12%) of the product were obtained, mp. 81-83 ^about S.

 Found,%: C 66.62; H 7.77; N, 7.75.

C ₂₀ H ₂₈ N ₂ O ₄
Calculated,%: C 66.64; H 7.83; N, 7.77.

 PRI me R 14. Erythro-N- {1,3-dihydro-1- [6- (1-octinyl) -2-pyridinyl] -2-propanyl} acetamide.

To ethyl erythro-2-acetamido-3-hydroxy-3- [6- (1-octinyl) -2-pyridinyl] propionate (9.02 g) in anhydrous tetrahydrofuran (80 ml) was slowly added 2.0 M lithium borohydride / tetrahydrofuran (12.5 ml) at ⁰ ° C under a nitrogen atmosphere. The mixture was stirred overnight at room temperature, then it was cooled and methanol and water (1: 1) were added slowly, followed by the addition of glacial acetic acid 1.5 ml in a mixture of methanol with water (1: 1, 15 ml) until pH 6 ,8. The resulting solution was stirred at room temperature for 1.5 hours, and the residue was subjected to azeotropy with methanol (4 × 40 ml). The residue was suspended in 7.5% sodium bicarbonate solution (25 ml, pH 8.5), saturated sodium chloride solution (25 ml), extracted with a mixture of trichloromethane and 2-propanol (3: 1) and concentrated. The residue was flash chromatographed on silica gel, eluting with a mixture of ethyl acetate and 0.5% methanol. The appropriate fractions were collected and evaporated. The residue was recrystallized (3 times) from ethyl acetate, and 1.24 g (15.6%) of the product was obtained, so pl. 81-83 ^about S.

 Found,%: C 68.03; H 7.97; N, 8.70.

C ₁₈ H ₂₆ N ₂ O ₃
Calculated,%: C 67.90; H 8.23; N, 8.80.

 PRI me R 15. Ethyl-erythro-2-acetamido-3- [6- (1-hexadecinyl) -2-pyridinyl] -3-hydroxypropionate.

A solution of 6- (1-hexadecynyl) -2-pyridinecarboxaldehyde (17.4 g), acetamidomalonic acid monoethyl ester (10.6 g) and triethylamine (5.4 ml) in anhydrous tetrahydrofuran (85 ml) was stirred for 3 hours at room temperature in a nitrogen atmosphere. Then the reaction mixture was evaporated, and the residue was dissolved in ethyl acetate. The solution was washed with a half-saturated sodium chloride solution, dried over anhydrous magnesium sulfate, filtered, and the filtrate was evaporated. The residue was purified by flash chromatography on silica gel, eluting with a mixture of hexane and ethyl acetate in a gradient (2: 1 - 1: 1). The appropriate fractions were collected and evaporated. The residue was recrystallized from ethanol, and then from 85% ethanol to obtain 12.8 g (50.9%) of the product, mp. 82.5-84 ^about S.

 Found,%: C 70.86; H, 9.18; N, 5.82.

C ₂₈ H ₄₄ N ₂ O ₄
Calculated,%: C 71.15; H 9.38; N, 5.93.

 Example 16. Erythro-N- {1- [6- (1-dodecynyl) -2-pyridinyl] -1,3-dihydroxy-2-propanyl} acetamide.

To a solution of ethyl erythro-2-acetamido-3- [6- [1-dodecyl) pyridinyl] -3-hydroxypropionate (20.3 g) in anhydrous tetrahydrofuran (250 ml) was added 2.0 M lithium borohydride / tetrahydrofuran (30 mL) at ⁰ ° C under a nitrogen atmosphere. The reaction mixture was stirred overnight at room temperature. The mixture was cooled and methanol and water (1: 1) were slowly added, followed by the addition of glacial acetic acid (3.5 ml) in a mixture of methanol and water (1: 1, 50 ml) until a pH of 6.5 was obtained. The solution was stirred for 2 hours at room temperature, then the solvents were evaporated, and the residue was subjected to azeotropy with methanol (5 x 100 ml). The residue was then suspended in a 7.5% sodium bicarbonate solution (65 ml, pH 8.5), extracted into a 3: 1 mixture of chloroform and 2-propanol, and then concentrated. The residue was flash chromatographed on silica gel, eluting with a mixture of 0.5% methanol and ethyl acetate. The appropriate fractions were collected and evaporated. After recrystallization of the residue from a mixture of hexane and ethyl acetate (1: 1), 15.5 g (85.0%) of the product are obtained, mp. 86-88 ^about S.

 Found,%: C 70.78; H 9.35; N, 7.49.

C ₂₂ H ₃₄ N ₂ O ₃
Calculated,%: C 70.55; H 9.15; N, 7.48.

 PRI me R 17. Ethyl-erythro-2-acetamido-3- (6-decyl-2-pyridinyl) -3-hydroxypropionate.

Ethyl erythro-2-acetamido-3-6- (1-decynyl) -3-hydroxypropionate (2.7 g) in ethanol (65 ml) was recovered using 5% palladium charcoal (0.7 g) in a hydrogenator Parra at a hydrogen pressure of 275.76 kPa. After 2.5 hours, the catalyst was collected, the filtrate was evaporated, and the residue was recrystallized from ethyl acetate, whereby 2.11 g (77.6%) of the product was obtained, so pl. 67-68.5 ^about S.

 Found,%: C 66.96; H, 9.13; N, 7.08.

C ₂₂ H ₃₆ N ₂ O ₄
Calculated,%: C 67.32; H 9.24; N, 7.14.

Example 18. Erythro-N- {1- [6-decyl-2-pyridinyl) -1,3-dihydroxy] -2-propanyl} acetamide. Erythro-N- {1- [6- (1-decynyl) -2-pyridinyl] -1,3-dihydroxy-2-propanyl} acetamide (4.0 g) in ethanol (100 ml) was reduced using 5 % palladium carbon (0.1 g) in a Parr hydrogenator at a hydrogen pressure of 275.76 kPa. After 2 hours, the catalyst was collected, the solvent was evaporated, and the residue was recrystallized from ethyl acetate, whereby 3.69 g (91%) of the product were obtained, mp. 94-96 ^about S.

 Found,%: C 68.36; H 9.72; N, 7.94.

C ₂₀ H ₃₄ N ₂ O ₃
Calculated,%: C 68.54; H 9.78; N, 7.99.

 PRI me R 19. Treo-2-amino-1- (6-decyl-2-pyridinyl) -1,3-dihydroxypropane.

 Treo-N- {1- [6- (1-decyl) -2-pyridinyl] -1,3-diacetyloxy-2-propanyl} acetamide (1.0 g) in ethanol (55 ml) was reduced using 5% palladium coal (0.06 g) in a Parr hydrogenator at a hydrogen pressure of 275.76 kPa. After 2 hours, the catalyst was collected and the solvent was evaporated, yielding 0.95 g (94%) of threo-N- [3- (6-decyl-2-pyridinyl) -1,3-diacetyloxy-2-propanyl] acetamide .

Acetamide (0.95 g), hydrazine hydrate (40 ml) and ethanol (20 ml) were heated under reflux under nitrogen atmosphere for 25 hours. The reaction mixture was cooled, water (30 ml) was added and extracted with ethyl acetate. The ethyl acetate layer was washed with saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and the filtrate was evaporated. The residue was chromatographed on silica gel, eluting with a mixture of trichloromethane, methanol and 2N. ammonium hydroxides in a gradient of 980: 20: 2 - 970: 30: 2. The appropriate fractions were collected and evaporated. The residue was dissolved in ethyl acetate, washed with a half-saturated sodium chloride solution, dried, filtered. After evaporation of the filtrate gave 0.50 g (72%) of product, t.pl.76-78 ^C.

 Found,%: C 70.02; H 10.63; N, 8.85.

C ₁₈ H ₃₂ N ₂ O ₂
Calculated,%: C 70.02; H 10.46; N, 9.08.

PRI me R 20. Erythro-2-amino-1- (6-decyl-2-pyridinyl) -1,3-dihydroxypropane. Erythro-N- [1- (6-decyl-2-pyridinyl) -1,3-dihydroxy-2-propanyl] acetamide (6.0 g), hydrazine hydrate (60 ml) and ethanol (15 ml) were heated in a vessel reflux in the presence of nitrogen for 20 hours. The reaction mixture was cooled, water (75 ml) was added and the mixture was extracted with ethyl acetate. The ethyl acetate layers were washed with saturated sodium chloride solution, dried over anhydrous magnesium sulfate, filtered, and the filtrate was evaporated. The residue was combined with 1.44 g from two other experiments, and the combined product was chromatographed on silica gel, eluting with a mixture of trichloromethane, methanol and 2N. ammonium hydroxides in a gradient of 950: 50: 3 - 900: 100: 5. The appropriate fractions were collected and evaporated. The residue was dissolved in ethyl acetate (150 ml) and the solution was washed with half-saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and the filtrate was evaporated, yielding 5.60 g (79%) of product, t.pl.52-55 ^C.

 Found,%: C 69.63; H 10.29; N, 8.87.

C ₁₈ H ₃₂ N ₂ O ₂
Calculated,%: C 70.09; H 10.46; N, 9.08.

PRI me R 21. Ethyl-erythro-2-acetamido-3- (6-dodecyl-2-pyridinyl) -3-hydroxy-propionate. Ethyl erythro-2-acetamido-3- [6- (1-dodecynyl) -2-pyridinyl] -3-hydroxypropionate (2.0 g) in ethanol (80 ml) containing 5% palladium carbon (0, 06 g), was reduced in a Parr hydrogenator at a hydrogen pressure of 275.76 kPa. After 2 hours, the catalyst was filtered off, the filtrate was evaporated, the residue was recrystallized from ethyl acetate to give 1.42 g (70.3%) of product, t.pl.71-73 ^C.

 Found,%: C 68.74; H 9.46; N, 6.69.

C ₂₄ N ₄₀ N ₂ O ₄
Calculated,%: C 68.54; H 9.59; N, 6.66.

PRI me R 22. Erythro-N- [1- (6-dodecyl-2-pyridinyl) -1,3-dihydroxy-2-propanyl] acetamide. Erythro-N- {1- [6- (1-dodecynyl) -2-pyridinyl] -1,3-dihydroxy-2-propanyl} acetamide d (6.05 g) in ethanol (120 ml) containing 5 % palladium carbon (0.15 g) was reduced in a Parr hydrogenator at a hydrogen pressure of 206.82 kPa. After 2 hours, the catalyst was filtered off, the filtrate was evaporated, and the residue was recrystallized from ethyl acetate, whereby 5.90 g (96.4%) of the product was obtained, mp. 99-100.5 ^about C.

 Found,%: C 69.71; H 10.37; N, 7.34.

C ₂₂ H ₃₈ N ₂ O ₃
Calculated,%: C 69.80; H 10.12; N, 7.40.

PRI me R 23. Erythro-2-amino-1- (6-dodecyl-2-pyridinyl) -1,3-propanediol. Erythro-N- [1- (6-dodecyl-2-pyridinyl) -1,3-dihydroxy-2-propanyl] acetamide (3.8 g), hydrazine hydrate (35 ml) and ethanol (20 ml) were heated in a vessel reflux in the presence of nitrogen for 24 hours. The reaction mixture was cooled, water (50 ml) was added, and the resulting mixture was extracted with chloroform (3 x 65 ml). The extracts were washed with saturated sodium chloride solution, dried over anhydrous magnesium sulfate, filtered and the filtrate was evaporated. The residue was chromatographed on silica gel, eluting with a mixture of chloroform, methanol and 2N. ammonium hydroxide (950: 50: 3). The residue was dissolved in ethyl acetate, the solution was washed with a half-saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and filtered. The filtrate was evaporated, yielding 2.10 g (62%) of product, t.pl.61-64 ^C.

 Found,%: C 71.04; H 10.95; N, 8.07.

C ₂₀ N ₃₆ N ₂ O ₂
Calculated,%: C 71.38; H 10.78; N, 8.32
PRI me R 24. Erythro-N- [1- (6-hexyl-2-pyridinyl) -1,3-dihydroxy-2-propanyl] acetamide. Erythro-N- {1- [6- (1-hexynyl) -2-pyridinyl] -1,3-dihydroxy-2-propanyl} acetamide (5.80 g) in ethanol (125 ml) was hydrogenated using 0 , 15 g of 5% palladium-carbon in the Parr system at a pressure of 275.76 kPa. After 2.5 hours, the catalyst was collected, the filtrate was evaporated, and the residue was recrystallized from ethyl acetate, whereby 5.2 g (88.6%) of the product were obtained, mp. 75-76.5 ^about S.

 Found,%: C 68.18; H 8.78; N, 9.50.

C ₁₆ H ₂₆ N ₂ O ₃
Calculated,%: C 68.28; H, 8.90; N, 9.52.

PRI me R 25. N, O, O-Tribenzyloxycarbonyl-erythro-2-amino-1- (6-decyl-2-pyridinyl) -1,3-propane diol
Erythro-2-amino-1- (6-decyl-2-pyridinyl) -1,3-propanediol (1.50 g), N-benzyloxycarbonyloxyisuccinimide (4.00 g) and triethylamine (2.23 ml) in anhydrous tetrahydrofuran (60 ml) was stirred at room temperature under nitrogen for 9 days. Then, further N-benzyloxycarbonyloxy-succinimide (4.00 g) was added and stirring continued for 3 days, after which the reaction mixture was evaporated. The residue was dissolved in ethyl acetate, the solution was washed with saturated sodium chloride, dried over anhydrous magnesium sulfate, filtered, and the filtrate was evaporated. The residue was purified by flash chromatography on silica gel, eluting with a mixture of hexane and ethyl acetate (9: 1). The appropriate fractions were collected and evaporated to give 1.87 g (54%) of the product.

 Found,%: C 71.00; H 6.92; N, 3.77.

C ₄₂ N ₅₀ N ₂ O ₈
Calculated,%: C 70.96; H 7.09; N, 3.94.

 PRI me R 26. Ethyl erythro-2-acetamido-3-hydroxy-3- [3- (1-undecynyl) phenyl] propionate.

To a solution of 3-bromobenzaldehyde (30.3 g) and 1-undecine (29.5 g) in triethylamine (120 ml) was added bis (triphenylphosphine) palladium (II) chloride (1.9 g), followed by copper iodide (I ) (0.25 g). The mixture was stirred in a dark room for 6 hours at 55 ^{° C} and under a nitrogen atmosphere. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate and filtered. The filtrate was washed with water and a saturated solution of sodium chloride, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated, whereby 45.8 g of 3- (1-undecynyl) benzaldehyde was obtained as an oily substance.

A solution of 3 (1-undecynyl) benzaldehyde (23.0 g), acetamidomalonic acid monoethyl ester (15.1 g) and triethylamine (11.2 ml) in anhydrous tetrahydrofuran (150 ml) was stirred for 48 hours at room temperature in nitrogen atmosphere. Then another 7.6 g of acetamidomalonic acid monoethyl ester and 5.6 ml of triethylamine were added and stirring continued for 72 hours. The reaction mixture was evaporated and the residue was purified on silica gel columns, eluting with a mixture of hexane and ethyl acetate (2: 1), in resulting in 13.0 g (41%) of the product. The resulting product was dissolved in a warm mixture of water and ethanol 3: 2. The precipitate was collected. The filtrate was concentrated, and the precipitate was recrystallized from cyclohexane, whereby an analytical sample was obtained, mp. 69-71 ^about S.

 Found,%: C 71.81; H, 8.72; N 3.51.

C ₂₄ H ₃₅ NO ₄
Calculated,%: C 71.79; H, 8.79; N, 3.49.

 PRI me R 27. Ethyl erythro-2-acetamido-3- [3- (1-dodecynyl) phenyl] 3-hydroxypropionate.

To a solution of 3-bromobenzaldehyde (26.5 g) and 1-dodecin (25.0 g) in triethylamine (105 ml) was added bis (triphenylphosphine) palladium (II) chloride (1.9 g) and then copper iodide (I ) (1.9 g). The mixture was stirred in the dark at 55 ^{° C} and under a nitrogen atmosphere. The reaction mixture was diluted with ethyl acetate and filtered. The filtrate was washed with water and a saturated sodium chloride solution, dried over anhydrous magnesium sulfate, filtered and concentrated, whereby 37.7 g of 3- (1-dodecynyl) benzaldehyde was obtained, and the filtrate was obtained as an oily product.

A solution of 3- (1-dodecynyl) benzaldehyde (7.6 g), acetamidomalonic acid monoethyl ester (5.1 g) and triethylamine (3.8 ml) in anhydrous tetrahydrofuran (35 ml) was stirred at room temperature under nitrogen in within 48 hours. An additional 2.6 g of acetamidomalomonic acid monoethyl ester and 1.9 ml of triethylamine were then added, and the mixture was stirred for 72 hours. The mixture was evaporated and the residue was purified on silica gel columns, eluting with a mixture of hexane and ethyl acetate (2: 1 ), and received 4.8 g (43%) of the product. The product was dissolved in a warm mixture of ethanol and water (3: 2), and then cooled. The precipitate was collected. The filtrate was concentrated, and the residue was recrystallized from a mixture of ethyl acetate and hexane (1: 2), whereby an analytical sample was obtained, mp. 80-82 ^about S.

 Found,%: C 72.34; H 8.74; N, 3.38.

C ₂₅ H ₃₇ NO ₄
Calculated,%: C 72.26; H, 8.97; N, 3.37.

Example 28. Cis-erythro-N- {1- [6-dodecenyl) -2-ciridinyl] -1,3-dihydroxy-2-propanyl} acetamide. Erythro-N- {1- [6- (1-dodecynyl) -2-pyridinyl] -1,3-dihydroxy-2-propanyl} acetamide id (2.05 g) in ethanol (55 ml), 5% palladium barium sulfate (0.02 g) and 0.04 g of quinoline were hydrogenated at atmospheric pressure until 1 eq. hydrogen (approx. 123 ml). The catalyst was filtered off, the filtrate was evaporated, and the residue (2.1 g) was combined with the residue (3.5 g) from similar reactions. The combined residues were chromatographed on silica gel, eluting with a mixture of hexane and ethyl acetate in a gradient of 1: 2 - 1: 4, and 1.58 g (58%) of the product was obtained, mp. 96-98 ^about S.

 Found,%: C 70.17; H 9.67; N, 7.43.

C ₂₂ H ₃₆ N ₂ O ₃
Calculated,%: C 70.18; H 9.64; N, 7.44.

 PRI me R 29. 5- (1-Dodecynyl) -2-thiophenecarboxaldehyde.

A solution of 1-dodecin (28.7 g), 5-bromo-2-thiophenecarboxaldehyde (300 g) and triethylamine (47.7 g) in anhydrous tetrahydrofuran (75 ml) was degassed and stirred at room temperature and under nitrogen atmosphere. Then bis (triphenylphosphine) palladium (II) chloride was added to the mixture, followed by the addition of copper (I) iodide. The mixture was degassed and stirred for 3 hours at room temperature and under nitrogen. The precipitate was collected and washed with ethyl acetate and the filtrate was evaporated. The residue was distilled in an oven (oven temperature 175 ° ^C / 0.1 mm Hg) to give 27.1 g (62%) of product as an oil. Part of this product was purified by flash chromatography on silica gel eluting with a mixture of hexane and dichloromethane (7: 3), and dried for 3 hours ^at 50 ° C in vacuo to give an analytical sample.

 Found,%: C 73.86; H, 8.72.

C ₁₇ H ₂₄ OS
Calculated,%: C 73.86; H, 8.75.

 Example 30. Ethyl erythro-2-acetamido-3- [5- (1-dodecynyl) -2-thienyl] -3-hydroxypropionate.

A suspension of 5-dodecynyl-2-tiofenekarboksaldegida (31.8 g), monoethyl ester acetamidomalonic acid (21.7 g) and anhydrous tetrahydrofuran (150 ml) was degassed and cooled ^to 0 ° C was added triethylamine (5% excess ), the solution was degassed and the reaction mixture was stirred for 2 days at room temperature and in a nitrogen atmosphere. An additional 21.7 g of acetamidomalonic acid monoethyl ester and 5% excess of triethylamine were then added, and the reaction mixture was stirred at room temperature for 5 days under nitrogen. The mixture was evaporated and the residue was purified by flash chromatography on silica, eluting with a mixture of ethyl acetate and hexane (1: 1). The appropriate fractions were collected and evaporated. The residue was recrystallized from ethyl acetate-hexane to obtain 29.5 g (61%) of the product, mp. 81-83 ^about S.

 Found,%: C 65.36; H, 8.25; N, 3.30.

C ₂₃ H ₃₅ NO ₄ S
Calculated,%: C 65.53; H 8.37; N, 3.32.

 PRI me R 31. Erythro-N- [1- [5- (1-dodecynyl) -2thienyl] -1,3-dihydroxy-2-propanyl} acetamide.

A solution of ethyl erythro-2-acetamido-3- [5- (1-dodecynyl) -2-thienyl] -3-gidroksipropio- nata (15.0 g) in anhydrous tetrahydrofuran (150 ml) was stirred at ⁰ ° C under an atmosphere nitrogen, while adding dropwise 2M lithium borohydride in tetrahydrofuran (22.3 ml). The reaction mixture was stirred for 3 days at room temperature in a nitrogen atmosphere. The pH of the mixture was adjusted to 6 with glacial acetic acid, after which the mixture was evaporated. The residue was diluted with water (100 ml) and extracted with ethyl acetate. The combined organic extracts were dried over anhydrous magnesium sulfate, filtered, and the filtrate was evaporated. The residue was purified by flash chromatography on silica, eluting with 1-5% methanol-ethyl acetate. The residue was recrystallized from ethyl acetate-hexane and 9.6 g (71%) of the product were obtained, mp. 83-85 ^about S.

 Found,%: C 66.47; H 9.53; N, 3.75.

C ₂₁ H ₃₃ NO ₃ S
Calculated,%: C 66.45; H 8.76; N, 3.69.

 PRI me R 32. Erythro-2-amino-1- [5- (1-dodecynyl) -2-thienyl] -1,3-propanediol.

A solution of erythro-N- {1- [5- (1-dodecynyl) -2-thienyl] -1,3-dihydroxy-2-propanyl} acetamide (3.00 g), 2N. sodium hydroxide (100 ml) and 95% ethanol was stirred overnight at 65 ^C. After cooling to room temperature the mixture was evaporated and the residue diluted with sodium bicarbonate solution (250 ml). The mixture was extracted with a mixture of chloroform and isopropanol (3: 1), and the organic layers were combined, dried over anhydrous magnesium sulfate, filtered, and the filtrate was evaporated. The residue was purified by flash chromatography on silica gel, eluting with a mixture of dichloromethane, methanol and hydroxy ammonium (90: 9: 1). The appropriate fractions were combined and evaporated. The residue was crystallized from ethyl acetate / hexane to give 1.4 g (53%) of product, mp. 77-78 ^about S.

 Found,%: C 67.61; H, 8.63; N, 4.16.

C ₁₉ H ₃₁ NO ₂ S
Calculated,%: C 67.61; H 9.26; N, 4.15.

 PRI me R 33. Erythro-N- [1- [5-dodecyl) -2-thienyl] -1,3-dihydroxy-2-propane] acetamide.

A mixture of erythro-N- [1- [5- (1-dodecyl) -2-thienyl] -1,3-dihydroxy-2-propyl] acetamide (8.00 g), 5% palladium carbon (400 mg) and absolute ethanol (500 ml) was vigorously stirred, while shaking, in a Parr hydrogenator for 3 hours at a hydrogen pressure of 344.7 kPa. The catalyst was collected. Fresh catalyst (400 mg) was added to the filtrate, and the mixture was again vigorously stirred while stirring overnight at a hydrogen pressure of 344.7 kPa. After that, the mixture was filtered through a celite pad, and the filter cake was washed with ethanol. The filtrate was evaporated and the precipitate was recrystallized from ethyl acetate, whereby 7.3 g (90%) of the product was obtained, mp. 104-106 ^about S.

 Found,%: C 65.45; H 9.58; N, 3.67.

C ₂₁ H ₃₇ NO ₃ S
Calculated,%: C 65.75; H 9.72; N, 3.65.

 PRI me R 34. Erythro-2-amino-1- [5- (1-dodecyl) -2-thienyl] -1,3-propanediol.

Solution of erythro-N- {3- [5- (1-dodecyl) -2-thienyl] -1,3-dihydroxy-2-propyl} acetamide (3.00 g), hydrazine monohydrate (35 ml) and absolute ethanol (25 ml) was stirred at ⁷⁰ ° C and in an atmosphere of nitrogen for 48 hours. The reaction mixture was cooled to room temperature, poured into 300 ml of dilute sodium bicarbonate solution (300 ml) and extracted with chloroform. The combined organic layers were dried with anhydrous sodium sulfate, and the filtrate was evaporated. The residue was purified by flash chromatography on silica (dichloromethane: methanol: ammonium hydroxide = 90: 9: 1). The appropriate fractions were combined and evaporated. The residue was recrystallized from ethyl acetate / hexane to give 1.4 g (52%) of product, mp. 89-90 ^about S.

 Found,%: C 66.48; H 10.37; N, 4.11.

C ₁₉ H ₃₅ NO ₂ S
Calculated,%: C 66.81; H 10.33; N, 4.10.

 PRI me R 35. Ethyl-erythro-2-acetamido-3- (3-dodecyl-5-isoxazolyl) -3-hydroxypropionate.

A mixture of 3-dodecyl-5-izoksazolkarboksaldegida (5.72 g) and monoethyl ester atsetaminomalonovoy acid (4.06 g) in anhydrous tetrahydrofuran (75 ml) was cooled ^to 0 ° C with stirring, and triethylamine (2.29 d). The solution was evaporated, and the residue was purified by flash chromatography (silica gel, ethyl acetate: hexane = 2: 1). The appropriate fractions were collected and evaporated. After recrystallization of the residue from ethyl acetate / hexane, 4.65 g (52.6%) of the product were obtained, mp. 87-89 ^about S.

 Found,%: C 64.55; H 9.08; N, 6.76.

C ₂₂ H ₃₈ N ₂ O ₅
Calculated,%: C 64.36; H 9.33; N, 6.82.

 PRI me R 36. Erythro-N- {1- [3- (1-dodecyl) -5-isoxazolyl] -1,3-dihydroxy-2-propyl] acetamide.

To a solution of freshly prepared calcium borohydride (0.61 g) from calcium hydride and borane-dimethyl sulfide in dry tetrahydrofuran (70 ml) was added a solution of ethyl erythro-2-acetamido-3- (3-dodecyl-5-isoxazolyl) -3-hydroxypropionate (2 4 g) in anhydrous tetrahydrofuran (20 ml). The reaction mixture was stirred at room temperature for 3 hours. The reaction was quenched by the addition of a mixture of water, methanol and acetic acid (90: 10: 5) and extracted with chloroform. The solution was evaporated and the residue recrystallized twice from ethyl acetate / hexane to give 1.23 g (57.1%) of product, t.pl.88-90 ^C.

 Found,%: C 65.17; H 9.60; N, 7.60.

C ₂₀ N ₃₆ N ₂ O ₄
Calculated,%: C 65.19; H 9.85; N, 7.60.

 PRI me R 37. Ethyl erythro-2-acetamyl-2- (6-bromo-2-pyridinyl) -3-hydroxypropionate.

A solution of 6-bromo-2-pyridinecarboxaldehyde (5.6 g), acetamidomalonic acid monoethyl ester (5.67 g) and triethylamine (4.2 ml) in anhydrous tetrahydrofuran (40 ml) was stirred at room temperature and under nitrogen atmosphere for nights. The reaction mixture was evaporated and purified on a silica gel column, eluting with a mixture of hexane and ethyl acetate (1: 1), whereby 7.9 g (80%) of the product was obtained as a mixture of diastereoisomers. Recrystallization from toluene and then from ethyl acetate gave 2.15 g (21.6%) of the erythro product, mp 98-100 ^about S.

 Found,%: C 43.56; H 4.53; N, 8.42.

C ₁₂ H ₁₅ BrN ₂ O ₄
Calculated,%: C 43.52; H 4.57; N, 8.46.

 PRI me R 38. Erythro-N- [1- (6-bromo-2-pyridinyl) -1,3-dihydroxy-2-propanyl] acetamide.

By erythro: threo 2: 1 mixture of ethyl 2-acetamido-3- (6-bromo-2-pyridinyl) -3-hydroxy-propionate 11.4 g in anhydrous tetrahydrofuran (60 ml) was slowly added at ⁰ ° C and in a nitrogen atmosphere of 2.0 M lithium borohydride / tetrahydrofuran (20.6 ml), and the resulting mixture was stirred at room temperature overnight. After this, the mixture was cooled and methanol and water (1: 1, 100 ml) were slowly added, and then glacial acetic acid (2 ml) was added to adjust the pH to 6.5. The mixture was evaporated and the residue was azeotroped with methanol (6 x 50 ml). The residue was suspended in a 7.5% sodium bicarbonate solution (40 ml), (pH 8.5), extracted with trichloromethane / isopropanol 3: 1, filtered, and the filtrate was concentrated. The residue was then flash chromatographed on silica gel, eluting with a mixture of ethyl acetate and methanol (19: 1), to give 8.9 g (93.7%) of the product. After recrystallization from ethanol, an analytical sample of an erythro-diastereomer was obtained, mp. 134.5-136.5 ^about S.

 Found,%: C 41.64; H 4.54; N, 9.64.

C ₁₀ H ₁₃ BrN ₂ O ₃
Calculated,%: C 41.54; H 4.53; N 9.69.

 PRI me R 39. 6- (1-Hexadecinyl) -2-pyridinecarboxaldehyde.

A solution of 6-bromo-2-pyridinecarboxaldehyde (12.3 g), 1-hexadecin (16.1 g), triethylamine (20.0 g), bis (triphenylphosphine) palladium (II) chloride (0.92 g) and iodide copper (I) (0,13 g) in anhydrous tetrahydrofuran (55 ml) was heated for 29 hours at 50 ° ^C under a nitrogen atmosphere. After that, the reaction mixture was cooled to room temperature, filtered, and the filter cake was washed with ethyl acetate. The filtrate was evaporated and the residue was dissolved in ethyl acetate (100 ml). The mixture was washed with a solution of water and saturated sodium chloride (1: 1), dried over anhydrous magnesium sulfate, filtered, and the filtrate was evaporated. The residue was flash chromatographed on silica gel, eluting with a mixture of 1% ethyl acetate and hexane. The appropriate fractions were collected and evaporated. The residue was dissolved in ethyl acetate, and the solution was washed with a half-saturated sodium chloride solution, dried over anhydrous magnesium sulfate, filtered and the filtrate was evaporated, whereby 11.5 g (53.5%) of the product were obtained, mp. 38-40 ^about C.

 Found,%: C 80.44; H 10.00; N, 4.30.

C ₂₂ H ₃₃ NO
Calculated,%: C 80.68, H 10.16; N, 4.28.

 PRI me R 40. 3- (1-Dodecyl) -5-isoxazolemethanol.

To a solution of 1-nitrotridecane (10.5 g) and O-trimethisilylpropinol (5.88 g) in anhydrous benzene (100 ml) was added dropwise a solution of freshly distilled phenylisocyanate (10.9 g) and triethylamine (5.56 g) in anhydrous benzene (40 ml) at 40 ^about C, while stirring mechanically. The mixture was heated to ⁶⁰ ° C for 3.5 hours and filtered. The filtrate was evaporated, dissolved in tetrahydrofuran (300 ml) and 1.0 M tetrabutylammonium fluoride (8 ml) was added. After 30 minutes, the mixture was evaporated, and the residue was purified by flash chromatography (silica gel, 2% methanol: dichloromethane). The appropriate fractions were collected and evaporated, whereby 10.5 g (86%) of the product were obtained, mp. 61-63 ^about S.

 Found,%: C 71.92; H 11.10; N, 5.19.

C ₁₆ H ₂₉ NO ₂
Calculated,%: C 71.87; H 10.93; N, 5.24.

 PRI me R 41. 3- (1-Dodecyl) -5-isoxazole carboxaldehyde.

Osalilhlorida solution (28.8 ml) in anhydrous dichloromethane (100 ml) was cooled to ^-60 ° C and added first a solution of dimethylsulfoxide (8.9 ml) in dichloromethane (30 ml) and the suspension of 3- (1-dodecyl) - 5-isoxazolemethanol (14.0 g) in anhydrous dichloromethane (200 ml). The resulting mixture was stirred at ^-60 ° C for 1 h, quenched with triethylamine (87 ml) and allowed to warm to room temperature whereupon the solution was poured into water (300 ml) and extracted with dichloromethane. The organic phases were washed with dilute citric acid solution, dried, filtered and the filtrate was evaporated. The residue was passed through a narrow layer of silica gel using dichloromethane as eluent. The solution was evaporated and the residue was recrystallized from a mixture of ether and hexane, whereby 11.5 g (78%) of the product was obtained, mp. 53-54 ^about S.

 Found,%: C 72.22; H 10.59; N, 5.24.

C ₁₆ H ₂₇ NO ₂
Calculated,%: C 72.41; H 10.25; N, 5.28.

PRI me R 42. Erythro-N- {1- [6- (1-hexadicinyl) -2-pyridinyl] -1,3-dihydroxy-2-propanyl} acetates
To ethyl-erythro-2-acetamido-3-6- (1-hexadecynyl) -2-pyridinyl-3-hydroxypropiono-one (11.1 g) in anhydrous tetrahydrofuran (100 ml), 2.0 M lithium borohydride was slowly added / tetrahydrofuran (11.8 ml) at ⁰ ° C and under a nitrogen atmosphere. The reaction mixture was stirred 2.5 h at room temperature, cooled and a mixture of water and ethanol (1: 1, 60 ml) and glacial acetic acid (1.4 ml) were slowly added until the pH was 6.5. The mixture was then stirred 0.5 h at room temperature and evaporated. The residue was azeotroped with methanol (4 x 40 ml), suspended with a 7.5% sodium bicarbonate solution (25 ml), pH 8.5, and the mixture was extracted with a mixture of chloroform and 2-propanol (3: 1). The solution was concentrated, and the residue was flash chromatographed on silica gel (ethyl acetate = 99: 1). The appropriate fractions were collected, evaporated. After recrystallization, 8.57 g (84.4%) of the product are obtained, mp. 88-90 ^about S.

 Found,%: C 72.55; H 0.46; N, 6.54.

C ₂₆ H ₄₂ N ₂ O ₃
Calculated,%: C 72.52; H 9.83; N, 6.51.

 PRI me R 43. Erythro-N- [1,3-diacetyloxy-1- (6-hexadecyl-2-pyridinyl) -2-propanyl] acetamide.

A mixture of N- {1- [6- (1-hexadecynyl) -2-pyridinyl] -1,3-dihydroxy-2-propanyl} acetamide (7.26 g mixture of erythro: threo = 5: 2), acetic anhydride (10.5 g), triethylamine (15.5 g) and 4-dimethylaminopyridine (0.21 g) in tetrahydrofuran (100 ml) were stirred overnight at room temperature. Thereafter, the reaction mixture was evaporated, methanol added and heated ^at 50 ° C for 20 minutes and then concentrated. To the residue was added a 7.5% sodium bicarbonate solution until the pH was 8.5. The resulting mixture was extracted with chloroform. The organic extract was dried over anhydrous magnesium sulfate, and the filtrate was concentrated. The residue was flash chromatographed (hexane: ethyl acetate = 2: 1 to 1: 1). The appropriate fractions were collected, evaporated to give 5.54 g (64%) of erythro-N- [1,3-diacetyloxy-1- (6-hexadecyinyl-2-pyridinyl) -2-propanyl] acetamide.

A mixture of erythro-N- [1,3-diacetyloxy-1- (6-hexadecynyl-2-pyridinyl-2-propanyl] acetamide (5.4 g) in ethanol (150 ml) and 5% palladium carbon (0.20 g ) were vigorously stirred in a Parr hydrogenator at a hydrogen pressure of 241.29 kPa for 2.5 hours. The catalyst was collected and the filtrate was evaporated. The residue was chromatographed to obtain 4.1 g (75%, 48% of the total product), mp 79 -80.5 ^about C.

 Found,%: C 69.81; H 9.60; N, 5.41.

C ₃₀ N ₅₀ N ₂ O ₅
Calculated,%: C 69.46; H 9.72; N, 5.40.

 PRI me R 44. Erythro-N- [1- (6-hexadecinyl-2-pyridinyl) -1,3-dihydroxy-2-propanyl] acetamide.

A mixture of erythro-N- {1- [6- (1-hexadecynyl) -2-pyridinyl] -1,3-dihydroxy-2-propanyl} acetamide (3.9 g), ethanol (125 ml) and 5% palladium coal (0.20 g) was shaken in a Parr hydrogenator at a pressure of 241.29 kPa for 2 hours. The catalyst was collected and the filtrate was evaporated. The residue was recrystallized from ethyl acetate to give 3.6 g (91%) of product, mp. 98-101 ^about S.

 Found,%: C 71.92; H 10.75; N, 6.52.

C ₂₆ H ₄₆ N ₂ O ₃
Calculated,%: C 71.85; H 10.67; N, 6.44.

 PRI me R 45. Erythro-2-amino (6-hexadecyl-2-pyridinyl) -1,3-propanediol.

Erythro-N- [1- (6-hexadecyl-2-pyridinyl) -1,3-dihydroxy-2-propanyl] acetamide (3.0 g), hydrazine hydrate (35 ml) and ethanol (25 ml) were heated in a reflux vessel in the presence of nitrogen for 28 hours. The reaction mixture was cooled, water (40 ml) was added, and the mixture was extracted with chloroform. The combined extracts were washed with saturated sodium chloride solution, dried over anhydrous magnesium sulfate, filtered, and the filtrate was evaporated. The residue was chromatographed on silica gel, eluting with a mixture of chloroform, methanol and 2N. ammonium hydroxide (950: 50: 3). The appropriate fractions were collected and concentrated. The residue was dissolved in ethyl acetate, and the solution was washed with a half-saturated sodium chloride solution, dried over anhydrous magnesium sulfate, filtered and the filtrate was evaporated. The residue was subjected to azeotropy with toluene and 1.37 g (50%) of the product was obtained, mp. 67-69 ^about S.

 Found,%: C 73.25; H 11.14; N, 7.04.

C ₂₄ H ₄₄ N ₂ O ₂
Calculated,%: C 73.42; H, 11.30; N, 7.13.

 PRI me R 46. Ethyl-threo-2-acetamido-3- (6-bromo-2-pyridinyl) -3-hydroxypropionate.

A solution of 6-bromo-2-pyridinecarboxaldehyde (30.3 g), acetamidomalonic acid monoethyl ester (34.1 g) and triethylamine (16.6 g) in anhydrous tetrahydrofuran (170 ml) was stirred in the presence of nitrogen at room temperature for nights. The reaction mixture was concentrated and the residue was azeotroped three times with ethyl acetate and then recrystallized from ethyl acetate to remove 36.4 g of ethyl erythro-2-acetamido-3- (6-bromo-2-pyridinyl) -3-hydroxypropionate. The filtrate was chromatographed on silica gel (hexane: ethyl acetate = 3: 2 - 1: 1). The appropriate fractions were collected and concentrated. The residue was recrystallized from ethyl acetate to give 1.0 g (2.0%) of product, mp. 144-146 ^about S.

 Found,%: C 44.02; H 4.52; N, 8.39.

C ₁₂ H ₁₅ BrN ₂ O ₄
Calculated,%: C 43.52; H 4.57; N, 8.46.

 PRI me R 47. 6- (1-Undecynyl) pyridine-2-carboxaldehyde.

Solution of 6-bromopyridin-2-carboxaldehyde (15.0 g), 1-undecine (12.9 g), triethylamine (24.5 g), bis (triphenylphosphine) palladium (II) chloride (1.1 g, 2% ) and copper iodide (I) (0,15 g, 1%) in anhydrous tetrahydrofuran (60 ml) was heated under nitrogen for 10 hours at 55 ^C. The reaction mixture was filtered, the filter cake washed with ethyl acetate and the filtrate evaporated. The residue was dissolved in ethyl acetate, and the solution was washed with a half-saturated sodium chloride solution, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated. The residue was flash chromatographed on silica gel, eluting with 0-2% ethyl acetate: hexane. The appropriate fractions were collected and evaporated to give 17.5 g (84.0%) of the product.

 Found,%: C 79.03; H 9.36; N, 5.14.

C ₁₇ H ₂₃ NO
Calculated,%: C 79.33; H 9.01; N, 5.44.

 PRI me R 48. Ethyl erythro-2-acetamido-3-hydroxy-3- [6- (1-undecynyl) -2-pyridinyl] propionate.

A mixture of ethyl erythro-2-acetamido-3- (6-bromo-2-pyridinyl) -3-hydroxypropionate (20.8 g), 1-undecine (11.5 g), triethylamine (12.7 g), chloride bis (triphenylphosphine) palladium (0.88 g) and copper iodide (0.12 g) in dry tetrahydrofuran (100 ml) was heated at 55 ° ^C under nitrogen for 4 hours. Then, at room temperature was added an additional 2.9 g of 1- undecine, 3.2 g of triethylamine, 0.44 g of palladium bis (triphenylphosphine) chloride and 0.06 g of copper iodide, after which the reaction mixture was heated for another 5 hours. The mixture was then evaporated and the residue was dissolved in ethyl acetate. The solution was washed with semi-saturated sodium chloride, and the organic phase was flash chromatographed on silica gel (hexane: ethyl acetate = 3: 2-1: 1). The appropriate fractions were collected and evaporated. Recrystallization of the residue from ethyl acetate gave 16.0 g (63.4%) of the product, mp. 92-93 ^about S.

 Found,%: C 68.58; H 8.54; N, 6.94.

C ₂₃ H ₃₄ N ₂ O ₄
Calculated,%: C 68.63; H 8.51; N, 6.96.

 PRI me R 49. Erythro-N- {1,3-dihydroxy-1- [6- (1-undecynyl) -2-pyridinyl] -2-pro-panyl} acetates d.

To ethyl erythro-2-acetamido-3-hydroxy-3- [6- (1-undecynyl) -2-pyridinyl] propionate (17.9 g) in anhydrous tetrahydrofuran (150 ml) was added 2.0 M lithium borohydride / tetrahydrofuran (22 mL) at 0 ^C and under nitrogen. Then the reaction mixture was cooled, stirred overnight at room temperature, and first water with methanol (1: 1) (30 ml) was added, and then glacial acetic acid (2.8 ml) in a mixture of methanol with water (1: 1) ( 30 ml) until the pH is 6.4. The resulting solution was stirred at room temperature for 1 h, then evaporated and the residue was subjected to azeotropy with methanol. After that, the residue was suspended with a 7.5% sodium bicarbonate solution (pH 8.5), extracted with chloroform and 2-propanol (3: 1) and concentrated. The residue was flash chromatographed on silica gel (0.5-1% methanol: ethyl acetate). The appropriate fractions were collected and concentrated. After recrystallization of the residue from a mixture of hexane and ethyl acetate (1: 1), 12.1 g (75.4%) of the product are obtained, mp. 95-96.5 ^about S.

 Found,%: C 69.84; H 8.87; N, 7.71.

C ₂₁ H ₃₂ N ₂ O ₃
Calculated,%: C 69.97; H 8.95; N, 7.77.

 Example 50. (Z) -Erythro-N- {1,3-dihydroxy-1- [6- (1-octenyl) -2-pyridinyl] -2-propanyl} acetamide.

A solution of ethyl erythro-2-acetamido-3- [6- (1-octanyl) -2-pyridinyl] -3-hydroxypropionate (9.9 g) in dry tetrahydrofuran (80 ml) and 2.0 M lithium borohydride / tetrahydrofuran (12.5 ml) was stirred at ⁰ ° C under nitrogen. Then the reaction mixture was stirred at room temperature overnight, cooled and a mixture of methanol and water (1: 1) (40 ml) was added, and acetic acid (1.5 ml) was added until a pH of 6.8 was obtained. After that, the reaction mixture was stirred for 1 h, evaporated, and the residue was subjected to azeotropy with methanol. Then a 7.5% sodium bicarbonate solution was added until a pH of 8.5 was obtained. The mixture was extracted with chloroform: 2-propanol (3: 1) and concentrated. The residue was flash chromatographed on silica gel eluting with 1% methanol / ethyl acetate to give 7.6 g of product.

A portion of the obtained product (5.0 g) and 8.35 g from another similar experiment, 25.7 g of acetic anhydride, 38.2 g of triethylamine and 0.51 g of 4-dimethylaminopyridine in tetrahydrofuran (180 ml) were stirred for 3 hours at room temperature. The reaction mixture was evaporated, methanol was added, the resulting mixture was heated ^at 50 ° C for 20 minutes and evaporated. Then a 7.5% sodium bicarbonate solution was added until a pH of 8.5 was obtained, and the resulting mixture was extracted with chloroform. The extract was dried over anhydrous magnesium sulfate, filtered and the filtrate was concentrated. The residue was flash chromatographed (hexane: ethyl acetate = 2: 1). The appropriate fractions were collected and concentrated to give (Z) -erythro-N- {1,3-diacetyloxy-1- [6- (1-octenyl) -2-pyridinyl] -2-propanyl} acetate amide
A solution of this compound (1.1 g), potassium carbonate (0.44 g) in methanol (18 ml) was stirred for 1 h. The reaction mixture was filtered and the filtrate was concentrated. The residue was chromatographed on silica gel 0.5% methanol / ethyl acetate. The appropriate fractions were collected and concentrated, whereby 0.5 g (3.7%) of the product was obtained.

 Found,%: C 67.60; H 8.96; N, 8.72.

C ₁₈ H ₂₈ N ₂ O ₃
Calculated,%: C 67.47; H 8.81; N, 8.74.

 PRI me R 51. Erythro-N- [1,3-diacetyloxy-2- (6-octyl-2-pyridinyl) -2-propanyl] acetamide.

Solution of erythro-N- {1,3-dihydroxy-1- [6- (1-octynyl) -2-pyridinyl] -2-propanyl} acetamide (13.4 g), acetic anhydride (25.7 g ), triethylamine (38.2 g) and 4-dimethylaminopyridine (0.51 g) in tetrahydrofuran (180 ml) was stirred at room temperature for 3 hours. The reaction mixture was evaporated, methanol was added to the residue, and the resulting solution was heated ^at 50 ° C 20 min and evaporated. After this, a 7.5% sodium bicarbonate solution was added until a pH of 8.5 was obtained, and the resulting mixture was extracted with chloroform. The extract was dried over anhydrous magnesium sulfate, filtered and the filtrate was concentrated. The residue was flash chromatographed (hexane: ethyl acetate = 2: 1 to 1: 1). The appropriate fractions were collected, evaporated to give 9.17 g of erythro-N- [1,3-diacetyloxy-1- (6-octynyl-2-pyridinyl) -2-propanyl] acetamide.

Part of this compound (7.5 g) in ethanol (200 ml) and 0.25 g of 5% palladium charcoal were agitated in a Parr hydrogenator at a hydrogen pressure of 275.76 kPa. After 1.5 hours, the catalyst was collected and the filtrate was evaporated. The residue was chromatographed to give 6.0 g (78.5%, 43% total) of product, mp. 53-56 ^about S.

 Found,%: C 65.07; H 8.32; N, 6.88.

C ₂₂ H ₃₄ N ₂ O ₅
Calculated,%: 65.00; H 8.43; N, 6.89.

 PRI me R 52. Erythro-N- [1,3-dihydroxy-1- (6-octyl-2-pyridinyl) -2-propanyl] acetamide.

A solution of erythro-N- [1,3-diacetyloxy-1- (6-octyl-2-pyridinyl-2-propanyl] acetamide (5.2 g) and potassium carbonate (0.88 g) in methanol (75 ml ) was stirred for 1 h. The precipitate was collected and the filtrate was evaporated, then a 7.5% solution of sodium bicarbonate and 1N hydrochloric acid were added until pH 8.5, and then the mixture was extracted with a mixture of chloroform and 2-propanol (3: 1). The extract was dried over anhydrous magnesium sulfate, filtered and the filtrate was evaporated. recrystallization of the residue from ethyl acetate gave 3.1 g (75.6%) of product, m.p. 85-86,5 ° ^C.

 Found,%: C 66.98; H 9.74; N, 8.65.

C ₁₈ H ₃₀ N ₂ O ₃
Calculated,%: C 67.05; H 9.38; N, 8.69.

 PRI me R 53. Erythro-2-amino-1- (6-octyl-2-pyridinyl) 1,3-propanediol.

A solution of erythro-N- [1,3-dihydroxy-1- (6-octyl-2-pyridinyl) -2-propanyl] acetamide (3.8 g), hydrazine hydrate (35 ml) and ethanol (25 ml) was heated in a vessel under reflux for 26 hours. Then the reaction mixture was cooled, water (50 ml) was added and the mixture was extracted with chloroform. The extract was washed with saturated sodium chloride, dried over anhydrous magnesium sulfate, filtered and the filtrate was evaporated. The residue was chromatographed on silica gel (chloroform: methanol: 2N. Ammonium hydroxide = 950: 50: 3). The appropriate fractions were collected and evaporated. The residue was dissolved in ethyl acetate, and the solution was washed with a half-saturated sodium chloride solution, dried over anhydrous magnesium sulfate, filtered and the filtrate was evaporated. The residue was subjected to azeotropy with toluene and 2.47 g (75%) of the product were obtained, mp. 38-40 ^about C.

 Found,%: C 67.88; H 10.18; N, 9.74.

C ₁₆ H ₂₈ N ₂ O ₂ ˙ 0.1 N ₂ O
Calculated,%: C 68.10; H 10.07; N, 9.93.

 PRI me R 54. Treo-2-amino-1- (6-octyl-2-pyridinyl) -1,3-propanediol.

 A mixture of erythro- and threo-N- {1,3-dihydroxy-1- [6- (1-octinyl) -2-pyridinyl] -2-propanyl} acetamide (13.4 g), acetic anhydride (25 , 7 g), triethylamine (38.2 g) and 4-dimethylaminopyridine (0.5 g) in tetrahydrofuran (180 ml) were stirred for 3 hours at room temperature. Then the reaction mixture was evaporated, and the residue was heated with methanol (80 ml) for 20 min, and the resulting mixture was evaporated. Then a 7.5% sodium bicarbonate solution was added until a pH of 8.5 was obtained, and the resulting solution was extracted with chloroform. The extracts were dried, filtered and the filtrate was evaporated. The residue was flash chromatographed. The appropriate fractions were collected and evaporated, whereby 2.4 g (14%) of threo-N- {1,3-diacetyloxy-1- [6- (1-octinyl) -2-pyridinyl] -2-propanyl was obtained } acetamide. 2.4 g of this compound in ethanol (75 ml) containing 0.12 g of 5% palladium charcoal were vigorously stirred in a Parr hydrogenator at a pressure of 275.76 kPa. After 3 hours, the reaction mixture was filtered and the filtrate was evaporated. The residue was flash chromatographed. The appropriate fractions were collected and evaporated to give 2.2 g (92%) of threo-N- {1,3-diacetyloxy-1- [6-octyl-2-pyridinyl] -2-propane} acetamide.

A solution of threo-N- [1,3-diacetyloxy-1- (6-octyl) -2-pyridinyl) -2-propanyl] acetamide (2.17 g) was stirred with potassium carbonate (70 mg) and methanol (25 ml) for 1 h at room temperature, filtered, and the filtrate was evaporated. Then water was added, the pH was adjusted to 8.5, and the mixture was extracted with a mixture of chloroform and 2-propanol (3: 1). The extract was concentrated to give 1.6 g (94%) of threo-N- [1,3-diacetyloxy-1- (6-octyl-2-pyridinyl] -2-propanyl] acetamide, mp 71.5 -74 ^about S.

A solution of 1.6 g of the obtained compound, 15 ml of hydrazine hydrate and ethanol (15 ml) was heated under reflux in the presence of nitrogen for 23 hours. The reaction mixture was cooled, then water was added and the mixture was extracted with chloroform. The extracts were washed with saturated sodium chloride solution, dried over anhydrous magnesium sulfate, filtered and the filtrate was evaporated. The residue was chromatographed on silica gel (chloroform: methanol: 2N. Ammonium hydroxide = 960: 40: 3). The appropriate fractions were collected and evaporated, resulting in a gain of 0.78 g (56.5%, 7.0% in total) of the product, so pl. 74-77 ^about S.

 Found,%: C 68.48; H 10.15; N, 9.96.

C ₁₆ H ₂₈ N ₂ O ₂
Calculated,%: C 68.53; H 10.06; N, 9.99.

 PRI me R 55. Erythro-2-amino-1- (6-hexyl-2-pyridinyl) -1,3-propanediol.

 A solution of erythro-2- [1- (6-hexyl-2-pyridinyl) -1,3-dihydroxy-2-propanyl] acetamide (3.6 g), hydrazine hydrate (35 ml) and ethanol (25 ml) was heated in a reflux vessel in the presence of nitrogen for 29 hours. The reaction mixture was cooled, water (50 ml) was added and extracted with ethyl acetate. The extracts were washed with saturated sodium chloride solution, dried over anhydrous magnesium sulfate, filtered and the filtrate was evaporated. The residue was chromatographed on silica gel (chloroform: methanol: 2N. Ammonium hydroxide = 950: 50: 3). The appropriate fractions were collected and evaporated. The residue was dissolved in ethyl acetate (80 ml), and the solution was washed with a half-saturated sodium chloride solution, dried, filtered, and the filtrate was evaporated, whereby 2.02 g (66%) of the product was obtained.

 Found,%: C 65.91; H 9.42; N, 10.82.

C ₁₄ H ₂₄ N ₂ O ₂
Calculated,%: C 66.63; H 9.59; N, 11.10.

 PRI me R 56. 6- (7-Phenyl-1-heptinyl) pyridine-2-carboxaldehyde.

A solution of 6-bromopyridin-2-carboxaldehyde (30.0 g), 7-phenyl-1-heptin (26.8 g), triethylamine (48.9 g), bis (triphenylphosphine) palladium (II) chloride (2,3 g, 2%) and copper iodide (0.31 g, 1%) in anhydrous tetrahydrofuran (100 ml) was heated under nitrogen at 55 ^C for 70 h. The reaction mixture was cooled to room temperature, filtered and the filtrate was washed with ethyl acetate. Then the filtrate was evaporated. The residue was dissolved in ethyl acetate, the solution was washed with a half-saturated sodium chloride solution, dried with anhydrous magnesium sulfate, and the filtrate was concentrated. The residue was flash chromatographed on silica gel, eluting with 0.5-2% ethyl acetate: hexane. The appropriate fractions were collected and concentrated, whereby 29.5 g of product was obtained.

 Found,%: C 82.00; H 6.94; N, 5.02.

C ₁₉ H ₁₉ NO
Calculated,%: C 82.28; H 6.90; N, 5.05.

PRI me R 57. Ethyl-erythro-2-acetamido-2-hydroxy-3- [6- (7-phenyl-1-heptinyl) 2-pyridinyl] prop ion
A solution of 6- (7-phenyl-1-heptinyl) pyridin-2-carboxaldehyde (26.5 g), acetamidomalonic acid monoethyl ester (19.2 g), triethylamine (14.6 ml) in anhydrous tetrahydrofuran (125 ml) stirred for 3 days at room temperature in the presence of nitrogen. The reaction mixture was evaporated, the residue was dissolved in ethyl acetate, and the solution was washed with a semi-saturated sodium chloride solution, dried with anhydrous magnesium sulfate, filtered and evaporated. The residue was chromatographed on a silica gel column (hexane: ethyl acetate = 1: 1) to obtain 32.9 g (82.0%) of a mixture of erythro and threo isomers. After recrystallization of the mixture from hexane and ethyl acetate (1: 1), 4.7 g (11.5%) of the product are obtained, mp. 79-81 ^about S.

 Found,%: C 71.27; H 6.89; N, 6.63.

C ₂₅ H ₃₀ N ₂ O ₄
Calculated,%: C 71.07; H 7.16; N, 6.63.

 PRI me R 58. Erythro-N- {1,3-dihydroxy-1- [6- (7-phenyl-1-heptinyl) -2-pyridinyl] -2-propanyl} acetamide.

To a solution of ethyl erythro-2-acetamido-3-hydroxy-3- [6- (7-phenyl-1-heptinyl) -2-pyridinyl] propionate (23.4 g) in anhydrous tetrahydrofuran (200 ml) was added 2, 0 M lithium borohydride / tetrahydrofuran (22 mL) at ⁰ ° C under nitrogen. Then the reaction mixture was stirred at room temperature overnight, cooled and a mixture of methanol and water (1: 1, 50 ml) was added, followed by glacial acetic acid (2.5 ml) in methanol and water (11: 1, 30 ml) to obtain a pH of 6.4. The solution was stirred at room temperature for 1 h, evaporated, and the residue was subjected to azeotropy with methanol. The residue was suspended with sodium bicarbonate (40 ml, pH 8.5), saturated sodium chloride solution, then the mixture was extracted with chloroform and 2-propanol (3: 1). The extracts were concentrated. The residue was flash chromatographed on silica gel (0.5-5% methanol: ethyl acetate). The appropriate fractions were collected and evaporated. After recrystallization from a mixture of hexane and ethyl acetate (1: 1), 2.64 g (34%) of the product were obtained, mp. 83-85 ^about S.

 Found,%: C 72.75; H 7.66; N, 7.31.

C ₂₃ H ₂₈ N ₂ O ₃
Calculated,%: C 72.62; H 7.42; N, 7.36.

 PRI me R 59. Ethyl-erythro-2-acetamido-3-hydroxy-3- [6- (5-phenyl-1-pentinyl) -2-pyridinyl] propionate.

A mixture of ethyl erythro-2-acetamido-3- (6-bromo-2-pyridinyl) 3-hydroxypropionate (23.2 g), 5-phenyl-1-pentin (12.1 g), triethylamine (10.6 g ) chloride, bis (triphenylphosphine) palladium (0.98 g) and copper iodide (0.13 g) in anhydrous tetrahydrofuran (100 ml) was heated for 1.5 hours ^at 55 ° C in the presence of nitrogen. Then another 6.1 g of 5-phenyl-1-pentin, 7.1 g of triethylamine, 0.49 g of bis (triphenylphosphine) palladium chloride and 0.07 g of copper iodide were added, and the resulting reaction mixture was heated overnight. Then the reaction mixture was filtered and the filtrate was evaporated. The residue was dissolved in ethyl acetate, washed with a semi-saturated solution of sodium chloride and flash chromatography was performed on silica gel, eluting with a mixture of hexane and ethyl acetate (1: 1). The appropriate fractions were collected. The residue was again chromatographed, eluting with 1% methanol: chloroform, and 14.2 g (51.6%) of the product was obtained.

 Found,%: C 69.30; H 6.75; N, 6.94.

C ₂₃ H ₂₆ N ₂ O ₄
Calculated,%: C 70.03; H 6.64; N, 7.10.

 Example 60. Erythro-N- {1,3-dihydroxy-1- [6- (5-phenyl-1-pentynyl) -2-pyridinyl] -2-propanyl} acetamide.

To a solution of ethyl erythro-2-acetamido-3-hydroxy- (3- [6-5-phenyl-1-pentinyl) -2-pyridinyl] propionate 12.3 g in anhydrous tetrahydrofuran (100 ml) was added 2.0 M lithium borohydride / tetrahydrofuran (15.5 ml) at 0 ^C and under nitrogen. The reaction mixture was stirred at room temperature overnight, cooled and methanol and water (1: 1, 45 ml) and glacial acetic acid (1.8 ml) were added to obtain a pH of 6.5. The mixture was then stirred for 80 minutes at room temperature. After this, the reaction mixture was evaporated, the residue was subjected to azeotropy with methanol and suspended (7.5%) with sodium bicarbonate solution (25 ml, pH 8.5). The mixture was extracted with a mixture of chloroform and 2-propanol (3: 1), filtered, and the filtrate was concentrated. The residue was flash chromatographed on silica gel 0.5-1% methanol: ethyl acetate. The appropriate fractions were collected and concentrated, resulting in 6.0 g (54.6%) of the product, so pl. 91-95 ^about S.

 Found,%: C 71.48; H 6.75; N, 7.92.

C ₁₂ H ₂₄ N ₂ O ₃
Calculated,%: C 71.57; H 6.86; N, 7.95.

 Example 60. Erythro-N- {1,3-dihydroxy-1- [6- (5-phenyl-1-pentynyl) -2-pyridinyl] -2-propanyl} acetamide.

To a solution of ethyl erythro-2-acetamido-3-hydroxy- (3- [6-5-phenyl-1-pentynyl) -2-pyridinyl] propionate (12.3 g) in anhydrous tetrahydrofuran (100 ml) was added 2.0 M lithium borohydride / tetrahydrofuran (15.5 ml) at 0 ^C and under nitrogen. The reaction mixture was stirred at room temperature overnight, cooled and methanol and water (1: 1, 45 ml) and glacial acetic acid (1.8 ml) were added to obtain a pH of 6.5. The mixture was then stirred for 80 minutes at room temperature. After this, the reaction mixture was evaporated, the residue was subjected to azeotropy with methanol and suspended (7.5%) with sodium bicarbonate solution (25 ml, pH 8.5). The mixture was extracted with a mixture of chloroform and 2-propanol (3: 1), filtered, and the filtrate was concentrated. The residue was flash chromatographed on silica gel 0.5-1% methanol: ethyl acetate. The appropriate fractions were collected and concentrated, resulting in 6.0 g (54.6%) of the product, so pl. 91-95 ^about S.

 Found,%: C 71.48; H 6.75; N, 7.92.

C ₁₂ H ₂₄ N ₂ O ₃
Calculated,%: C 71.57; H 6.86; N, 7.95.

 PRI me R 61. Erythro-N- {1,3-dihydroxy-1- [6- (5-phenylpentin) -2-pyridinyl] -2-propanyl} acetamide hydrate.

 Erythro-N- {1,3-dihydroxy-1- [6- (5-phenyl-1-pentinyl-2-pyridinyl] -2-propanyl} acetamide (5.45 g) in ethanol (150 ml), containing 5% palladium charcoal (0.20 g) was vigorously stirred in a Parr hydrogenator at a hydrogen pressure of 275.76 kPa. After 1.5 h, the catalyst was collected. The filtrate was evaporated and the residue was chromatographed on silica gel (0.5-1% methanol: ethyl acetate) ), resulting in 2.8 g (50%) of the product.

 Found,%: C 67.95; H, 8.02; N, 7.53.

C ₂₁ H ₂₈ N ₂ O ₃ ˙ H ₂ O ₃
Calculated,%: C 67.36; H, 8.07; N, 7.48.

 Example 62. Erythro-2-amino-1- [6- (5-phenylpentyl) -2-pyridinyl] -1,3-propanediol hemihydrate.

The solution of erythro-N- {1,3-hydroxy-1- [6- (5-phenylpentin) -2-pyridinyl] -2-propanyl} acetamide (3.5 g), hydrazine hydrate (32 ml) and ethanol (25 ml ) was heated in a vessel under reflux in the presence of nitrogen for 26 hours. The reaction mixture was cooled, water (40 ml) was added, and the mixture was extracted with chloroform. The extracts were washed with saturated sodium chloride solution, dried over anhydrous magnesium sulfate, filtered and the filtrate was evaporated. A mixture of the residue and 0.25 g from a similar experiment was chromatographed on silica gel (chloroform: methanol: 2N. Ammonium hydroxide = 950: 50: 3). The appropriate fractions were collected and evaporated. The residue was dissolved in chloroform (100 ml), and the solution was washed with a saturated sodium chloride solution, dried over anhydrous magnesium sulfate, filtered, and the filtrate was evaporated. The residue was dried at ⁷⁰ ° C under high vacuum to afford 2.23 g (64%) of product.

 Found,%: C 70.77; H 8.23; N, 8.62.

C ₁₉ H ₂₆ N ₂ O ₂ ˙ 0.5 H ₂ O
Calculated,%: C 70.56; H 8.41; N, 8.66.

 PRI me R 63. Erythro-N- {1,3-dihydroxy-1- [3- (1-undecynyl) phenyl] -2-propanyl} acetamide.

To ethyl erythro-2-acetamido-3-hydroxy-3- [3- (1-undecynylphenyl] propionate (7.3 g) in dry tetrahydrofuran (75 ml) was added 2.0 M lithium borohydride / tetrahydrofuran (11.4 ml) at 0 ^C and under nitrogen. The reaction mixture was cooled, stirred at room temperature overnight and added dropwise to a mixture of glacial acetic acid (1.3 mL), methanol (25 ml) and water (25 ml) to obtain pH 6. The solution was then concentrated and the residue was extracted with ethyl acetate.The extracts were dried over anhydrous magnesium sulfate, filtered and the filtrate was concentrated. Iran residue with a mixture of ether and hexane (2: 3) and recrystallized from ethyl acetate to give 1.9 g (29%) of product, mp 99-101 ° ^C.

 Found,%: C 73.56; H 9.05; N, 3.93.

C ₂₂ H ₃₃ NO ₃
Calculated,%: C 73.50; H 9.25; N, 3.90.

 PRI me R 64. Erythro-N- {1- [3- (1-dodecyl) phenyl] -1,3-dihydroxy-2-propanyl} acetamide.

To ethyl erythro-2-acetamido-3 [3- (1-dodecynyl) phenyl] -3-hydroxypropionate (24.0 g) in tetrahydrofuran (220 ml) was added 2N. lithium borohydride / tetrahydrofuran (29 ml) at 2 ^{° C} under nitrogen. The reaction mixture was cooled, then stirred for 2.5 hours at room temperature, and a mixture of methanol and water (1: 1, 100 ml) and glacial acetic acid (3.3 ml) was added until a pH of 6.5 was obtained. After that, the solution was stirred at room temperature for 0.5 h, evaporated and the residue was subjected to azeotropy with methanol. The residue was then suspended in a 7.5% sodium bicarbonate solution (50 ml, pH 8.5) and the mixture was extracted with chloroform and propanol (3: 1). The extract was concentrated. The residue was flash chromatographed on silica gel, eluting with ethyl acetate. The appropriate fractions were collected and evaporated. Recrystallization of the residue from ethyl acetate gave 9.13 g (42.4%) of the product, mp. 93-95 ^about S.

 Found,%: C 73.66; H, 9.14; N, 3.69.

C ₂₃ H ₃₅ NO ₃
Calculated,%: C 73.96; H 9.44; N, 3.75.

 PRI me R 65. Erythro-N- [1- (3-dodecinophenyl) -1,3-dihydroxy-2-propanyl] acetamide.

Erythro-N- [1- (3-dodecyl) phenyl] -1,3-di-hydroxy-2-propanyl acetamide (4.4 g) in ethanol (100 ml) containing 5% palladium carbon (0.02 g ), vigorously shaken in a Parr hydrogenator at a pressure of 241.29 kPa for 2.5 hours. The catalyst was collected, the solvent was evaporated, and the residue was recrystallized from ethyl acetate, whereby 4.1 g (90.6%) of the product were obtained, i.e. pl. 101-104 ^about S.

 Found,%: C 72.82; H 10.36; N, 3.54.

C ₂₃ H ₃₉ NO ₃
Calculated,%: C 73.17; H 10.41; N, 3.71.

 PRI me R 66. Erythro-2-amino-1- (3-dodecylphenyl) -1,3-propanediol.

Erythro-N- [1- (3-dodecylphenyl) -1,3-dihydroxy-2-propanyl] acetamide (2.9 g), hydrazine hydrate (25 ml) and ethanol (25 ml) were heated in a reflux vessel in the presence of nitrogen for 22 hours. The reaction mixture was washed with saturated sodium chloride solution, dried over anhydrous magnesium sulfate, filtered, and the filtrate was evaporated. The residue was chromatographed on silica gel (chloroform: methanol: 2N. Ammonium hydroxide = 950: 50: 3). The appropriate fractions were collected and evaporated. The residue was dissolved in ethyl acetate (75 ml), and the solution was washed with a half-saturated sodium chloride solution, dried over anhydrous magnesium sulfate, evaporated, and the residue was subjected to azeotropy with toluene, whereby 1.35 g (52%) of the product was obtained, mp. 36-40 ^about C.

 Found,%: C 75.14; H 11.18; N, 4.12.

C ₂₁ H ₃₇ NO ₂
Calculated,%: C 75.17, H 11.12; N, 4.17.

 PRI me R 67. Erythro-N- [1- [5- (1-dodecyl) -2-thienyl] -1,3-diacetoxy-2-propyl] acetamide.

Solution of erythro-N- [1- [5-11-dodecyl) -2-thienyl] -1,3-dihydroxy-2-propyl] acetamide (12.0 g), acetic anhydride (19.2 g) , triethylamine (28.4 g) and dimethylaminopyridine (0.4 g) in anhydrous tetrahydrofuran (150 ml) was stirred at room temperature for 3 hours. The reaction mixture was evaporated and the residue was dissolved in chloroform. The solution was washed with water, dried, filtered, and the filtrate was evaporated. The residue was dried and 13.6 g (93.5%) of the product were obtained, mp. 105-107 ^about S.

 Found,%: C 64.33; H, 8.92; N, 3.02.

C ₂₅ H ₄₁ NO ₅
Calculated,%; 64.21; H 8.84; N, 2.99.

 PRI me R 68. Ethyl erythro-2-acetamide-3-5- (1-noninyl) -2-thienyl-3-hydroxypropionate.

A suspension of 5-nonynyl-2-tiofenekarboksaldegida (40.0 g), monoethyl ester acetamidomalonic acid (32.3 g) and anhydrous tetrahydrofuran (150 ml) was degassed and cooled ^to 0 ° C was added triethylamine (18.2 g) , the solution was degassed, and the reaction mixture was stirred for 4 days at room temperature in the presence of nitrogen. Then, acetamidomalonic acid monoethyl ester (32.3 g) and triethylamine (18.2 g) were added, and the reaction mixture was stirred for 4 days at room temperature in the presence of nitrogen. After that, the mixture was evaporated and the residue was dried in vacuo. The residue was flash chromatographed (silica, ethyl acetate: hexane = 1: 1). The appropriate fractions were collected and evaporated. The residue was crystallized from ether, then recrystallized twice from ethyl acetate to give 40.2 g (62%) of the product, mp. 104-106 ^about S.

 Found,%: C 63.30; H 7.64; N, 3.71.

C ₂₀ H ₂₉ NO ₄
Calculated,%: C 63.30; H 7.70; N, 3.69.

 PRI me R 69. Erythro-N- [1- [5- (1-noninyl) -2-thienyl] -1,3-dihydroxy-2-propyl] acetamide.

A solution of ethyl erythro-2-acetamido-3- [5- (1-nonynyl) -2-thienyl] -3-gidroksipropiona- ma (40.0 g) in anhydrous tetrahydrofuran (150 ml) was stirred under nitrogen at ⁰ C, adding dropwise lithium borohydride (2.0 M in tetrahydrofuran. The reaction mixture was stirred overnight under nitrogen at room temperature. Then, a solution of methanol, water and acetic acid (50: 50: 8, 108 ml) was added. ), cooling in an ice bath. The solution was neutralized with glacial acetic acid and evaporated. The residue was diluted with water and extracted with ethyl acetate. The dyed organic extracts were dried over anhydrous sodium sulfate, filtered and the filtrate was evaporated.The residue was flash chromatographed (silica, 2-4% methanol: ethyl acetate). The appropriate fractions were collected and evaporated. The residue was recrystallized twice from ethyl acetate to obtain 29.9 g ( 84%) of product, mp 81-83 ° ^C.

 Found,%: C 64.04; H 8.17; N, 4.16.

C ₁₈ H ₂₇ NO ₃ S
Calculated,%: C 64.06; H, 8.06; N, 4.15.

 PRI me R 70. Erythro-2-amino-1- [5- (1-noninyl) -2-thienyl] -1,3-propanediol.

A solution of erythro-N- {1- [5- (noninyl) -2-thienyl] -1,3-dihydroxy-2-propyl} acetamide (16.4 g), 2N, sodium hydroxide (150 ml) and 95% ethanol (75 mL) was stirred overnight at 70 ^C. The reaction mixture was cooled to room temperature and acidified with glacial acetic acid. The solution was diluted with water (200 ml), made basic with sodium bicarbonate solution and cooled. The precipitate was collected and the filtrate was extracted with a mixture of chloroform and 2-propanol (4: 1). The combined organic extracts were dried over anhydrous sodium sulfate, filtered, and the filtrate was evaporated. The residue was combined with the precipitate and flash chromatography was carried out (silica, dichloromethane: methanol: ammonium hydroxide = 90: 9: 1), whereby 11.8 g (82%) of the product was obtained. A portion of the product was crystallized from ether to give an analytical sample, mp. 64-67 ^about S.

 Found,%: C 65.22; H 8.56; N, 4.76.

C ₁₆ H ₂₅ NO ₂ S
Calculated,%: C 65.05; H 8.53; N 4.74.

 PRI me R 71. Erythro-N- {1- [5- (1-nonyl) -2-thienyl] -1,3-dihydroxy-2-propyl} acetamide.

A mixture of erythro-N- {1- [5- (1-noninyl) -2-thienyl] -1,3-dihydroxy-2-propyl} acetamide (8.00 g), 5% palladium carbon (800 g) and absolute ethanol (500 ml) was vigorously stirred in a hydrogenator at a hydrogen pressure of 344.7 kPa overnight. The catalyst was filtered through a pad of celite, and the filtrate was washed with ethanol. The filtrate was evaporated and the residue was recrystallized twice from ethyl acetate to give 7.0 g (86%) of the product, mp. 98-100 ^about S.

 Found,%: C 63:03; H 9.14; N, 4.01.

C ₁₈ H ₃₁ NO ₃ S
Calculated,%: C 63.61; H 9.15; N, 4.1.

 PRI me R 72. 5- (6-Phenyl-1-hexynyl) -2-thiophanecarboxaldehyde.

A solution of 6-phenyl-1-hexine (30.6 g), 5-bromo-2-thiophenecarboxaldehyde (37.0) and triethylamine (58.7 g) in anhydrous tetrahydrofuran (75 ml) was degassed and stirred at room temperature in the presence of nitrogen. Then 2 M of bis (triphenylphosphine) palladium (II) chloride (2.7 g) was added, followed by 1 M of copper (I) iodide (0.4 g). The mixture was degassed and stirred at room temperature in the presence of nitrogen overnight. The precipitate was filtered and washed with ethyl acetate. The filtrate was evaporated. The residue was distilled to obtain 47.0 g (91%) of the product. A portion of the product (2 g) was flash chromatographed (sodium dioxide, toluene: hexane = 1: 1). The appropriate fractions were collected and evaporated. The residue was distilled at ¹⁷⁰ C / 0.07 mmHg and received an analytical sample in the form of oil.

 Found,%: C 75.54; H, 6.04.

C ₁₇ H ₁₆ OS
Calculated,%: C 76.08; H 6.01.

 PRI me R 73. Erythro-N- {1- [5- (6-phenyl-1-hexynyl) -2-thienyl] -1,3-dihydroxy-2-propyl} acetamide.

A solution of ethyl erythro-2-acetamido-3- [5- (6-phenyl-1-hexynyl) -2-thienyl] -3-hydroxypropionate (41.6 g) in anhydrous tetrahydrofuran (150 ml) was stirred at 0 ^o C in the presence of nitrogen, while adding a solution of lithium borohydride 2.0 M in tetrahydrofuran (66 ml) dropwise. The reaction mixture was warmed to room temperature and stirred for 4 hours in the presence of nitrogen. Then, while cooling in an ice bath, a solution of methanol, water and acetic acid (50: 50: 8, 108 ml) was added. After this, glacial acetic acid was added and the solution was evaporated. Water was added to the residue, and the solution was extracted with ethyl acetate. The combined organic extracts were dried over anhydrous sodium sulfate, filtered, and the filtrate was evaporated. The residue was flash chromatographed (silica, dichloromethane: methanol: 2N. Ammonium hydroxide = 90: 9: 1). The appropriate fractions were cooled and evaporated. Recrystallization from ethyl acetate gave 31.5 (84%) of the product, mp. 131-133 ^about S.

 Found,%: C 67.54; H 6.88; N, 3.71.

C ₂₁ H ₂₅ NO ₃ S
Calculated,%: C 67.90; H 6.78; N, 3.77.

 PRI me R 74. Erythro-2-amino-1- [5- (6-phenyl-1-hexynyl) -2-thienyl] -1,3-propanediol.

A solution of erythro-N- {1- [5- (6-phenyl-1-hexynyl) -2-thienyl] -1,3-dihydroxy-2-propyl} acetamide (10.0 g), 1N. a solution of sodium hydroxide (125 ml) and 95% ethanol (75 ml) was stirred overnight at 65 ^about C. The reaction mixture was evaporated, and the residue was neutralized with glacial acetic acid. The solution was diluted with water (200 ml) and extracted with chloroform: 2-propanol (4: 1). The combined organic extracts were dried over anhydrous sodium sulfate, filtered, and the filtrate was evaporated. The residue was flash chromatographed (silica, dichloromethane: methanol: 2N. Ammonium hydroxide = 90: 9: 1). The appropriate fractions were collected and evaporated to give 7.8 g (88%) of the product. A portion of the product was crystallized from ethyl acetate and hexane to give an analytical sample, mp. 130-140 ^{° C} (dec.).

 Found,%: C 69.29; H 7.14; N, 4.26.

C ₁₉ H ₂₃ NO ₂ S
Calculated,%: C 69.27; H 7.04; N, 4.25.

 PRI me R 75. 4- (1-Dodecynyl) -2-thiophenecarboxaldehyde.

A solution of 1-dodecine (23.9 g), 5-bromo-2-thiophenecarboxaldehyde (25.0 g) and triethylamine (39.7 g) in anhydrous tetrahydrofuran (75 ml) was degassed and stirred at room temperature and in the presence of nitrogen. Then, 2 M bis (triphenylphosphine) palladium chloride (1.8 g) was added, followed by 1 M copper (I) iodide (0.25 g). The mixture was degassed and stirred for 3 days at room temperature and in the presence of nitrogen. The precipitate was filtered and the filter cake washed with ethyl acetate. The filtrate was evaporated and the residue was flash chromatographed (silica, hexane: dichloromethane = 7: 3). The appropriate fractions were collected and evaporated. The residue was dried ^at 50 ° C in vacuo for 3 h to give 35.5 g (98%) of product.

 Found,%: C 73.79; H 9.08.

C ₁₇ H ₂₄ OS
Calculated,%: C 73.86; H 8.75.

 Example 76. Ethyl erythro-2-acetamido-3- [4- (1-dodecynyl) -2-thienyl] -3-hydroxypropionate.

A suspension of 4- (1-dodecynyl) -2-tiofenekarboksaldegida (21.4 g), acetamidomalonic of the monoethyl ester (14.6 g) and anhydrous tetrahydrofuran (100 ml) was degassed and cooled ^to 0 ° C was added triethylamine (8 , 23 g), and the solution was degassed and the reaction mixture was stirred for 5 days at room temperature in the presence of nitrogen. Then, another 14.6 g of acetamidomalonic acid monoethyl ester and 8.23 g of triethylamine were added, and the resulting reaction mixture was stirred for 5 days at room temperature in the presence of nitrogen. After this, the mixture was evaporated, the residue was dried in vacuo and flash chromatography was performed (silica, hexane: ethyl acetate = 3: 2). The appropriate fractions were collected and evaporated. The residue was recrystallized from a mixture of ethyl acetate and hexane to give 23.3 g (71%) of product, t.pl.79-81 ^C.

 Found,%: C 65.63; H 7.96; N, 3.34.

C ₂₃ H ₃₅ NO ₄ S
Calculated,%: C 65.53; H 8.37; N, 3.32.

 PRI me R 77. Erythro-2-amino-1- [4- (1-dodecyl) -2-thienyl] -1,3-propanediol.

A solution of erythro-N- {1- [4- (dodecyl) -2-thienyl] -1,3-dihydroxy-2-propyl} acetamide (6.35 g), 2N. sodium hydroxide (100 ml) and 95% ethanol (50 ml) was stirred overnight at 65 ^C. The reaction mixture was cooled to room temperature and neutralized with glacial acetic acid. Then the solution was diluted with water (200 ml) and cooled. The precipitate was collected and the filtrate was extracted with chloroform. The combined organic extracts were dried over anhydrous sodium sulfate, filtered, and the filtrate was evaporated. The residue was combined with the precipitate and flash chromatographed (silica, dichloromethane: methanol: 2N ammonium hydroxide = 90: 9: 1). The appropriate fractions were collected and evaporated. The residue was recrystallized from ethyl acetate to give 4.1 g (73%) of product, mp. 99-100 ^about C.

 Found,%: C 66.70; H 10.40; N, 4.11.

C ₁₉ H ₃₅ NO ₂ S
Calculated,%: C 66.81; H 10.33; N, 4.10.

 PRI me R 78. Ethyl erythro-2-acetamido-3- [5- (6-phenyl-1-hexynyl) -2-thienyl] -3-hydroxypropionate.

A suspension of 6-phenyl-1-hexynyl-2-tiofenekarboksaldegida (45.0 g), monoethyl ester acetamidomalonic acid (31.7 g) and dry tetrahydrofuran (150 ml) was degassed and cooled to 0 ^C. Then was added 17.9 g of triethylamine, the resulting solution was degassed, and the reaction mixture was stirred for 2 days at room temperature in the presence of nitrogen. Then, another 31.7 g of acetamidomalonic acid monoethyl ester and 17.9 g of triethylamine were added, and the reaction mixture was stirred at room temperature in the presence of nitrogen for another 2 days. The mixture was evaporated, the residue was dried in vacuo and flash chromatography was performed (silica, ethyl acetate: hexane = 1: 1). The appropriate fractions were collected and evaporated. The residue was recrystallized from ethyl acetate-hexane to obtain 48.1 g (69%) of product, mp. 90-92 ^about S.

Found,%: C 66.48; H 6.59; N, 3.33;
C ₂₃ H ₂₇ NO ₄ S
Calculated,%: C 66.80; H 6.58; N, 3.39.

 PRI me R 79. Erythro-2-amino-1- [4- (1-dodecynyl) -2-thienyl] -1,3-propanediol acetate.

A solution of erythro-N- {1- [4-dodecynyl) -2-thienyl] -1,3-dihydroxy-2-propyl} acetamide (4.30 g), 2N. sodium hydroxide (100 ml), 95% ethanol 50 ml was stirred overnight at 65 ^about C. Then the reaction mixture was cooled to room temperature and acidified with glacial acetic acid. The solution was diluted with water (200 ml) and cooled in a refrigerator. The precipitate was collected and the filtrate was extracted with chloroform. The combined organic extracts were dried over anhydrous sodium sulfate, filtered, and the filtrate was evaporated. The residue was combined with the precipitate obtained previously and recrystallized twice from ethyl acetate to give 4.0 g (55%) of the product, mp. 120-122 ^about S.

Found,%: C 63.32; H 8.71; N, 3.50;
C ₂₁ H ₃₅ NO ₂ S
Calculated,%: C 63.44; H, 8.87; N, 3.52.

 PRI me R 80. Erythro-N- [1- [4- (1-dodecyl) -2-thienyl) 1,3-dihydroxy-2-propyl acetamide.

A mixture of erythro-N- {1- [4- (1-dodecynyl) -2-thienyl] -1,3-dihydroxy-2-propyl} acetamide (8.00 g), 5% palladium carbon (800 mg) and absolute ethanol (500 ml) was shaken at a hydrogen pressure of 344.7 kPa overnight. The reaction mixture was filtered through a pad of celite, and the filter cake was washed with ethanol. The solvent was evaporated and the residue was recrystallized twice from ethyl acetate to give 7.0 g (87%) of product, mp. 92-94 ^about S.

 Found,%: C 65.72; H 9.82; N, 3.63.

C ₂₁ H ₃₇ NO ₂ S
Calculated,%: C 65.75; H 9.72; N, 3.65.

 PRI me R 81. Erythro-2-amino-1- [3- (1-dodecyl) -5-isoxazolyl] -1,3-propanediol.

A solution of erythro-N- {1- [3-dodecyl) -5-isoxazolyl] -1,3-dihydroxy-2-propyl} acetamide (4.0 g), degassed 2n. sodium hydroxide solution (100 ml) and 95% ethanol (50 ml) was stirred for 3 hours at 60 ^C. The reaction mixture was concentrated, the residue diluted with sodium bicarbonate solution and extracted with chloroform: 2-propanol 4: 1. The combined organic extracts were dried over anhydrous magnesium sulfate, filtered and the filtrate was evaporated. The residue was recrystallized from ethyl acetate-hexane. The precipitate was flash chromatographed (silica, dichloromethane: ethanol = 90: 1). The appropriate fractions were collected and evaporated. The residue was recrystallized from ethyl acetate-hexane and 2.3 g (65%) of the product were obtained, mp. 88-90 ^about S.

 Found,%: C 65.55; H 10.44; N, 8.51.

C ₁₈ H ₃₄ N ₂ O ₃
Calculated: C, 66.22; H 10.50; N, 8.58.

 PRI me R 82. 3- (1-Dodecyl-5-isoxazolemethanol.

To a solution of 1-nitroundecane (38.0 g) and 0-trimethylsilylpropinol (24.1 g) in anhydrous benzene (300 ml) was added dropwise freshly distilled phenylisocyanate (44.9 g) and triethylamine (22.4 g) in anhydrous benzene (50 ml), stirring at 40 ^C. The reaction mixture was heated for 3 hours at 60 ° ^C, then cooled and filtered. 1.0 M tetrabutylammonium fluoride (40 ml) was added to the filtrate. After 30 minutes, the solution was evaporated, and the residue was flash chromatographed on silica gel (1% methanol-dichloromethane) to give 15.5 g (34%) of the product, mp. 55-56 ^about S.

 Found,%: C 70.44; H 10.42; N, 5.92.

C ₁₄ H ₂₅ NO ₂
Calculated,%: 70.25; H 10.53; N, 5.85.

 PRI me R 83. 3- (1-Decyl) -5-isoxazole carboxaldehyde.

To a solution of oxalyl chloride (31.7 ml) in anhydrous dichloromethane (100 mL) was cooled to ^-60 ° C, was added a solution of dimethylsulfoxide (9.8 ml) in dichloromethane (30 ml) and the suspension of 3- (1-decyl) - 5-isoxazolemethanol (13.8 g) in anhydrous dichloromethane (100 ml). The reaction mixture was stirred at ^-60 ° C for 0.5 hours and then quenched by the addition of triethylamine (40 ml) and allowed to warm to room temperature. The solution was poured into water (300 ml) and extracted with dichloromethane. The organic phases were washed with diluted citric acid, dried and evaporated. The residue was flash chromatographed (silica, dichloromethane: methanol = 50: 1). Suitable fractions were collected and evaporated. The residue was recrystallized from ether-hexane to give 11.2 g (82%) of product, mp. 46-48 ^about S.

 Found,%: C 71.16; H 9.93; N, 5.94.

C ₁₄ H ₂₃ NO ₂
Calculated,%: C 70.85; H 9.77; N, 5.90.

 PRI me R 84. Ethyl erythro-2-acetamido-3- (3- (1-decyl) -5-isoxazolyl) -3-hydroxypropionate.

To a mixture of 3- (decyl) -5-izoksazolkarboksaldegida (10 g), and acetamidomalonic of the monoethyl ester (7.9 g) in anhydrous tetrahydrofuran (100 ml) cooled ^to 0 ° C, was added triethylamine (4.5 g) in the presence of nitrogen. The solution was allowed to warm to room temperature, and then was stirred for 16 hours. The solution was evaporated, and the residue was recrystallized twice from ethyl acetate-hexane, and 10.3 g (64%) of the product was obtained, mp. 83-85 ^about S.

 Found,%: C 62.87; H 9.30; N, 7.32.

C ₂₀ H ₃₄ N ₂ O ₅
Calculated,%: C 62.80; H 8.96; N, 7.32.

 PRI me R 85. Erythro-2-amino-1- [3- (1-decyl) -5-isoxazolyl] -1,3-propanediol.

A solution of erythro-N- {1- [5- (decyl) -3-isoxazolyl] -1,3-dihydroxy-2-propyl} acetamide (9.30 g), degassed 2n. sodium hydroxide solution (200 ml), 95% ethanol (100 ml) was stirred for 6 hours at 80 ^C. The reaction mixture was concentrated, the residue diluted with sodium bicarbonate solution and extracted with a mixture of chloroform and 2-propanol = 4: 1. The combined organic extracts were dried over anhydrous magnesium sulfate, filtered and the filtrate was evaporated. The residue was flash chromatographed (silica, dichloromethane: methanol = 9: 1). The appropriate fractions were collected and evaporated. The residue was recrystallized from ethyl acetate-hexane to give 6.1 g (75%) of product, t.pl.88-90 ^C.

 Found,%: C 64.37; H 10.25; N, 9.42.

C ₁₆ H ₃₀ N ₂ O ₃
Calculated,%: C 64.40; H 10.13; N, 9.39.

 PRI me R 86. 5- (1-Undecynyl) -2-thiophenecarboxaldehyde.

A solution of 1-undecynyl (62.7 g), 5-bromo-2-tiofenekarboksaldegida (75.0 g) and triethylamine (119.2 g) in anhydrous tetrahydrofuran (300 ml) was degassed and stirred at ^0-5 ° C and nitrogen atmosphere. Then, 2 M bis (triphenylphosphine) palladium chloride (5.51 g) was added, followed by 1 M copper (I) iodide (0.75 g), and the mixture was degassed and stirred overnight at room temperature and in the presence of nitrogen. The precipitate was filtered and the filter cake washed with ethyl acetate. The filtrate was evaporated and the residue was purified by flash chromatography (silica, 5% ethyl acetate-hexane). The appropriate fractions were collected and evaporated to give 88.1 g (85%) of the product as an oily substance. This material was dried ^at 50 ° C under high vacuum (approx. 0.01 mm Hg) for 4 hours to obtain an analytical sample.

 Found,%: C 73.15; H 8.50.

C ₁₆ H ₂₂ OS
Calculated,%: C 73.23; H 8.45.

 Example 87. Ethyl erythro-2-acetamido-3- [5- (1-undecynyl) -2-thienyl] -3-hydroxypropionate.

A suspension of 5-undecynyl-2-tiofenekarboksaldegida (86.1 g), monoethyl ester acetamidomalonic acid (62.0 g) and anhydrous tetrahydrofuran (300 ml) was degassed and cooled ^to 0 ° C was added triethylamine (34.8 g) , the solution was again degassed, and the reaction mixture was stirred at room temperature and nitrogen atmosphere for 4 days. Thereafter, 62.0 g of acetamidoacetic acid monoethyl ester and 34.8 g of triethylamine were added, and the reaction mixture was stirred for another two days at room temperature and under nitrogen atmosphere. Then the mixture was evaporated, and the residue was dried in vacuo. The residue was purified by flash chromatography (silica, ethyl acetate: hexane = 1: 1). The appropriate fractions were collected and evaporated, and the residue was recrystallized from ethyl acetate to give 86.5 g (68%) of the product, mp. 80-82 ^about S.

 Found,%: C 64.65; H 8.07; N, 3.45.

C ₂₂ H ₃₃ NO ₄ S
Calculated,%: C 64.83; H 8.16; N, 3.44.

 PRI me R 88. Erythro-N- [1- [5- (1-undecinyl) -2-thienyl] -1,3-dihydroxy-2-propyl] acetamide.

A solution of ethyl erythro-2-acetamido-3- [5- (1-undecynyl) -2-thienyl] -3-gidroksipropio- tension (86.2 g) in anhydrous tetrahydrofuran (200 ml) was stirred at ⁰ ° C in the presence of nitrogen. Then, lithium borohydride (137.5 ml, 2, OM) in tetrahydrofuran) was added dropwise. The reaction mixture was allowed to warm to room temperature and then stirred for 4 hours in the presence of nitrogen. After that, the mixture was cooled in an ice bath. Then a solution of methanol, water and acetic acid (50 ml: 50 ml: 10 ml) was added. The solution was neutralized with glacial acetic acid. The mixture was evaporated and the residue was diluted with water (400 ml) and extracted with ethyl acetate. The combined organic extracts were dried over anhydrous sodium sulfate, filtered, and the filtrate was evaporated. The residue was purified by flash chromatography (silica, 7% methanol: dichloromethane). The appropriate fractions were collected and evaporated. Recrystallization of the residue from ethyl acetate gave 61.2 g (79%) of the product, mp. 88-90 ^about S.

 Found,%: C 66.00; H 8.71; N, 3.82.

C ₂₀ H ₃₁ NO ₃ S
Calculated,%: C 65.72; H 8.55; N, 3.83.

 PRI me R 89. (4-Trans) -N- [2,2-dimethyl-4- [5- (1-undecynyl) -2-thienyl] -1,3-5-yl] acetamide .

To a solution of erythro-N- {1- [5- (1-undecynyl) -2-thienyl] -1,3-dihydroxy-2-propyl} acetamide (25 g) in anhydrous acetone (400 ml) was added 2.2- dimethoxypropane (45.3 g) and a catalytic amount of para-toluenesulfonic acid. The solution was stirred at room temperature for 7 hours and then evaporated. The residue was purified by column chromatography (silica gel, chloroform: ether = 4: 1). The appropriate fractions were collected and concentrated. Recrystallization from ether-hexane gave 20.9 g (73.8%) of the product, mp. 88-89 ^about S.

 Found,%: C 68.26; H 8.83; N, 3.39.

C ₂₃ N ₃₅ NO ₃ S
Calculated,%: C 68.11; H 8.70; N, 3.45.

 PRI me R 90. Erythro-N- {1- [5- (1-noninyl) -2-thienyl] -1,3-dihydroxy-2-propyl} -1,1-dimethylethylcarbamate.

To a suspension of erythro-2-amino-1- [5- (1-noninyl) -2-thienyl] -1,3-propanediol (2.8 g) in a saturated solution of sodium bicarbonate (50 ml) was added a solution of di-tert- butyl dicarbonate (2.24 g) in chloroform (50 ml) for 2 minutes. The mixture was stirred for 45 min at ⁶⁰ ° C, then the layers were separated, and the organic layer was dried and evaporated. The residue was purified by passing it through a narrow pad of silica gel, and the filtrate was evaporated. The residue was crystallized from ether-hexane to give 2.9 g (77.6%) of the product, mp. 73-75 ^about S.

 Found,%: C 63.65; H 8.31; N, 3.50.

C ₂₁ H ₃₃ NO ₄ S
Calculated,%: C 63.77; H 8.41; N, 3.54.

 PRI me R 91. Erythro-2-amino-1- [5- (1-nonyl) -2-thienyl] -1,3-propanediol acetate.

A solution of erythro-N- {1- [5- (1-nonyl) -2-thienyl] -1,3-dihydroxy-2-propyl} acetamide (7.30 g), 2N. sodium hydroxide solution (100 ml) and 95% ethanol (75 ml) was stirred at 65 ° ^C overnight. Then the reaction mixture was concentrated, and the aqueous residue was neutralized with glacial acetic acid. The solution was diluted with water (200 ml) and was extracted with a mixture of chloroform and isopropanol (4: 1). The combined organic extracts were dried over anhydrous sodium sulfate, filtered, and the filtrate was evaporated. The residue was purified by flash chromatography (silica, dichloromethane: methanol: ammonium hydroxide = 90: 9: 1). The appropriate fractions were collected and concentrated. The residue was dissolved in ethanol and an excess of glacial acetic acid was added. Then ether and hexane were added. Recrystallization of the precipitate from ethyl acetate gave 4.1 g (53%) of the product, mp. 109-111 ^about S.

 Found,%: C 60.02; H 8.99; N, 3.90.

C ₁₈ H ₃₃ NO ₄ S
Calculated,%: C 60.13; H, 9.25; N, 3.90.

 PRI me R 92. Erythro-2-dimethylamino-2- [5- (6-phenyl-1-hexynyl) -2-thienyl] -1,3-propanediol.

 To a mixture of erythro-2-amino-1- [5- (6-phenyl-1-hexynyl) -2-thienyl] -1,3-propanediol (4.0 g), 37% aqueous formaldehyde (9.1 ml) and acetonitrile (50 ml) was added in three portions of sodium cyanoborohydride (2.29 g), while stirring at room temperature. After stirring for 30 minutes, glacial acetic acid (1 ml) was added dropwise and stirring continued for another 30 minutes. Then the mixture was neutralized with acetic acid and evaporated. 1N was added to the residue. sodium hydroxide (200 ml), and the mixture was extracted with chloroform. The extracts were dried with anhydrous sodium sulfate, filtered, and the filtrate was evaporated. The residue was flash chromatographed on silica gel, eluting with 10% methanol: dichloromethane. The appropriate fractions were collected and evaporated to give 1.3 g (30%) of the product as an oil.

 PRI me R 93. 4- (1-Dodecynyl) -2-thiophenecarboxaldehyde.

A solution of 1-dodecynyl (50.0 g), tributyltin hydride (109.4 g) and azobisisobutyronitrile (100 ml) was stirred for 3 hours at 95 ^C. The reaction mixture was cooled ^to 50 ° C and evaporated. The residue was filtered on a column of silica eluting with hexane. The appropriate fractions were collected and evaporated. The residue was dried in vacuo to give 131.7 g (96%) of tri-n-butyl-1-dodecenyl stannane.

To a solution of 4-bromo-2-thiophenecarboxaldehyde (35.0), tetrakis (triphenylphosphine) palladium (0) (4.23 g), 2,6-di-tert-butyl-4-methylphenol (several milligrams) and dry toluene (150 ml) was added dropwise tri-n-butyl-1-dodecenyl stannane (92.0 g) at room temperature and in the presence of nitrogen. The solution was heated in a reflux vessel for 4 hours while stirring. After cooling to room temperature, the solution was filtered through a pad of celite and the filter cake was taken up in ether. The filtrate was evaporated and the residue was purified by flash chromatography (silica, 5% ethyl acetate-hexane). The appropriate fractions were collected and concentrated. The residue was distilled in a ball oven (170 ° ^C / 0.3 mm Hg) to give 46.7 g (92%) of product as an oil (trans: cis = cca 4: 1).

 Found,%: C 73.64; H 9.62.

C ₁₇ H ₂₆ OS
Calculated,% C 73.33; H, 9.41.

 PRI me R 94. Ethyl erythro-2-acetamido-3- [5- (1-dodecenyl) -2-thienyl] 3-hydroxypropionate.

A suspension of 5-dodecenyl-2-tiofenekarboksaldegida (46.0 g, trans: cis = about 4:. 1, monoethyl ester acetamidomalonic acid (31.3 g) and anhydrous tetrahydrofuran (300 ml) was degassed and cooled to 0 ° ^C. Then triethylamine (17.6 g) was added, the solution was degassed, and the reaction mixture was stirred for 3 days at room temperature in the presence of nitrogen, then acetamidomalonic acid monoethyl ester (46.0 g) and triethylamine (17.6 g) were added, and the reaction the mixture was stirred at room temperature and in the presence of nitrogen for another three days. After the reaction mixture was concentrated and the residue was dried in vacuo, the residue was then purified by flash chromatography (silica, ethyl acetate: hexane = 2: 3). The appropriate fractions were collected and concentrated. The residue was recrystallized from diethyl ether to obtain 39 g (53%) of the product. (trans: cis = = approx. 4: 1), mp 66-68 ^о С.

 Found,%: C 65.36; H 8.71; N, 3.32.

C ₂₃ H ₃₇ NO ₄ S
Calculated,%: C 65.21; H 8.80; N, 3.31.

 PRI me R 95. Erythro-N- {1,3-diacetyloxy-1- [6- (5-phenyl-1-pentyl) -2-pyridinyl] - 2-propanyl} acetamide.

Diastereometric mixture of N- {1,3-dihydroxy-1- [6- (5-phenyl-1-pentinyl) -2-pyridinyl] -2-propanyl} acetamide (18.4 g, 6: 1-erythro- threo), acetic anhydride (31.9 g), triethylamine (47.5 g) and 4-dimethylaminopyridine (0.64 g) in tetrahydrofuran (200 ml) were stirred overnight at room temperature. The reaction mixture was concentrated, methanol was added, and the mixture was heated ^at 50 ° C for 20 min. After that, the mixture was evaporated and the residue was subjected to azeotropy with toluene. Then a 7.5% sodium bicarbonate solution was added until a pH of 8.5 was obtained, and the mixture was extracted into chloroform. The extract was dried over anhydrous magnesium sulfate, filtered and the filtrate was concentrated. The residue was combined with one of the residues from a similar reaction (8.0 g, 18.8 mmol) and purified by flash chromatography, eluting with a mixture of hexane and ethyl acetate = 1: 1. The appropriate fractions were collected and concentrated, whereby 5.06 g (16.3%) of the product were obtained, mp. 104-106 ^about S.

 Found,%: C 68.69; H, 6.47; N, 6.36.

C ₂₅ H ₂₈ N ₂ O ₅
Calculated,%: C 68.79; H 6.47; N, 6.42.

 PRI me R 96. Erythro-2-amino-1- [6- (5-phenyl-1-pentinyl) -2-pyridinyl] -1,3-pro-pandiol hemihydrate.

Erythro-N- {1,3-dihydroxy-1- [6- (5-phenyl-1-pentinyl) -2-pyridinyl] -2-propanyl} acetamide (4.4 g), 2N. hydroxide solution (100 ml) and ethanol (50 ml) was heated at 60 ° ^C under nitrogen for 13 hours. The reaction mixture was cooled, extracted with chloroform, and the extract was washed with half-saturated sodium chloride solution, dried over anhydrous magnesium sulfate, filtered, and the filtrate was evaporated. The residue was chromatographed twice on silica gel, eluting with a mixture of chloroform, methanol and 2N. sodium hydroxide (950: 50: 3 - 920: 80: 5). The appropriate fractions were collected and concentrated. The residue was dissolved in ethyl acetate and the solution washed with saturated sodium chloride, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated to give 1.13 g (36.5%) of product as an oily substance (dried at 60 ° ^C in vacuo )

 Found,%: C 71.87; H 7.11; N, 8.67.

C ₁₂ H ₂₂ N ₂ O ₂ ˙ 0.5 N ₂ O
Calculated,%: C 71.44; H 7.26; N, 8.77.

 PRI me R 97. Erythro-N- [1,3-dihydroxy-1- (6-undecyl-2-pyridinyl) -2-propanyl] acetamide.

A mixture of erythro-N- {1,3-dihydroxy-1- [6- (1-undecynyl) -2-pyridinyl] -2-propanyl} acetamide (5.4 g) in ethanol (125 ml) and 5% palladium carbon (0.20 g) was hydrogenated in a Parr hydrogenator at a hydrogen pressure of 275.76 kPa. After 2.5 hours, the catalyst was filtered and the filtrate was concentrated. Recrystallization from ethyl acetate gave 4.9 g (88.7%) of the product, mp. 97-98.5 ^about S.

 Found,%: C 69.19; H 9.91; N, 7.64.

C ₂₁ H ₃₆ N ₂ O ₃
Calculated,%: C 69.19; H 9.95; N, 7.68.

 PRI me R 98. Erythro-2-amino-1- (6-undecyl-2-pyridinyl) -1,3-propanediol.

Erythro-N- [1,3-dihydroxy-1- (6-undecyl-2-pyridinyl) -2-propanyl] acetamide (3.72 g), hydrazine hydrate (32 ml) and ethanol (25 ml) were heated in a vessel reflux in the presence of nitrogen for 24 hours. Then the reaction mixture was cooled, water was added, and the resulting mixture was extracted with chloroform. The extract was washed with saturated sodium chloride solution, dried over anhydrous magnesium sulfate, filtered and the filtrate was evaporated. The residue was chromatographed on silica gel (chloroform: methanol: 2N. Ammonium hydroxide = 950: 50: 3). The appropriate fractions were collected and evaporated. The residue was dissolved in chloroform, the solution was washed with a saturated sodium chloride solution, dried over anhydrous magnesium sulfate, filtered and the filtrate was concentrated, whereby 1.45 g (44%) of the product was obtained, mp. 56-59 ^{° C} (dried at 55 ° ^C in vacuo).

 Found,%: C 70.20; H 10.71; N, 8.48.

C ₁₉ H ₃₄ N ₂ O ₂
Calculated,%: C 70.76; H 10.63; N, 8.69.

 PRI me R 99. Erythro-2-amino-1- [6- (1-undecynyl) -2-pyridinyl] -1,3-propanediol hemihydrate.

Erythro-N- {1,3-dihydroxy-1- [6- (1-undecynyl) -2-pyridinyl] -2-propanyl} acetamide (5.4 g), 2N. sodium hydroxide (53 ml) and ethanol (35 ml) was heated 19 hours at ⁶⁰ ° C in the presence of nitrogen. Then, the reaction mixture was cooled, extracted with chloroform, and the extract was washed with a half-saturated sodium chloride solution, dried with anhydrous magnesium sulfate, filtered, and the filtrate was concentrated. The residue was chromatographed twice on silica gel (chloroform: methanol: 2N. Ammonium hydroxide = 950: 50: 3 - 930: 70: 5). The appropriate fractions were collected and concentrated to give 3.04 g (63.6%) of product as an oily substance (dried at 60 ° ^C in vacuo).

 Found,%: C 69.93; H 9.37; N, 8.46.

C ₁₉ H ₃₀ N ₂ O ₂ ˙ 5H ₂ O
Calculated,%: C 69.69; H 9.54; N, 8.55.

 PRI me R 100. Erythro-N- {1,3-diacetyloxy-1- [6- (1-undecynyl) -2-pyridinyl] 2-propanyl} acetamide.

Diastereometric mixture of N- {1,3-dihydroxy-1- [6- (1-undecynyl) -2-pyridinyl] - 2-propanyl} acetamide (12.0 g, erythro: threo = 4: 1), acetic anhydride (20.5 g), triethylamine (30.4 g) and 4-dimethylaminopyridine (0.41 g) in tetrahydrofuran (125 ml) were stirred overnight at room temperature. The reaction mixture was evaporated, methanol was added and the solution was heated for 20 minutes ^at 50 ° C and then evaporated. After this, a 7.5% sodium bicarbonate solution was added until a pH of 8.5 was obtained, and the mixture was extracted into chloroform. The extract was dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated. The residue was purified by flash chromatography, eluting with a mixture of hexane and ethyl acetate (1: 1). The appropriate fractions were combined, concentrated and received 3.5 g (24%) of the product, so pl. 69-71 ^about S.

 Found,%: C 67.65; H 8.23; N, 6.18.

C ₂₅ H ₃₆ N ₂ O ₅
Calculated,%: C 67.54; H 8.16; N, 6.30.

 PRI me R 101. 3- (1-Undecynyl) benzaldehyde.

A mixture of 3-bromobenzaldehyde (51.8 g), 1-undecine (48.6 g) bis (triphenylphosphine) palladium (II) chloride (3.37 g), copper iodide (457 mg) and triethylamine (196 ml) in anhydrous tetrahydrofuran (300 ml) was stirred for 4 hours at 55 ^C. The reaction mixture was filtered, the filtrate diluted with ethyl acetate and the solution washed with water and brine. The organic phase was dried over anhydrous magnesium sulfate, filtered and the filtrate was concentrated in vacuo. The residue was chromatographed over 300 g of silica gel (ethyl acetate: hexane = 1: 4). The appropriate fractions were collected and evaporated. After distillation of 40 g of a sample of the residue (81.3 g), 9.5 g (13%) of the product were obtained, b.p. 172-174 ^{° C} (at 0.5 mmHg).

 Found,%: C 84.76; H 9.57.

C ₁₈ H ₂₄ O
Calculated,%: C 84.32; H, 9.44.

 PRI me R 102. Erythro-2-amino-1- (3-undecynylphenyl) -1,3-propanediol acetate.

A solution of erythro-N- {1,3-diacetyloxy-1- [3- (undecynyl) phenyl] -2-propanyl} acetamide (2.76 g) and aqueous 2N. sodium hydroxide solution (62 ml) in ethanol (20 ml) was heated to ⁶⁰ ° C for 16 hours. The reaction mixture was cooled to room temperature and extracted with chloroform. The extract was dried over anhydrous magnesium sulfate, filtered and the filtrate was concentrated in vacuo. The residue was chromatographed on silica gel (chloroform: methanol: ammonium hydroxide = 900: 100: 5). The residue was again chromatographed (chloroform: methanol = 9: 1) to obtain 1.35 g (71%) of the free base.

To a solution of the free base (1.05 g) in dichloromethane (10 ml) was added glacial acetic acid (2 ml), followed by hexane (50 ml). The resulting mixture was concentrated in vacuo, and the solid residue was recrystallized from ethyl acetate, whereby 860 ml (69%) of the product was obtained, mp. 110-112 ^about C.

 Found,%: C 70.36; H 9.32; N, 3.69.

C ₂₂ H ₃₅ NO ₄
Calculated,%: C 69.99; H 9.34; N, 3.71.

 PRI me R 103. Erythro-2-amino-1- [3- (1-dodecynyl) phenyl] -1,3-propanediol acetate.

Erythro-N- {1,3-dihydroxy-1- [3- (1-dodecynyl) phenyl] -2-propanyl} acetamide (2.7 g), 2N. sodium hydroxide solution (36 ml) and ethanol (20 ml) was heated at ⁶⁰ ° C and under nitrogen for 19 hours. The reaction mixture was cooled and extracted with chloroform. The extract was washed with a semi-saturated sodium chloride solution, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated. The residue was chromatographed on silica gel, eluting with a mixture of chloroform, methanol and 2N. ammonium hydroxide (950: 50: 3). The appropriate fractions were collected and evaporated. The residue was dissolved in dichloromethane and treated with glacial acetic acid (0.27 ml). The mixture was concentrated in vacuo and the solid residue was recrystallized from ethyl acetate to give 1.72 g (61%) of product, t.pl.104-105,6 ^C.

 Found,%: C 70.62; H 9.46; N, 3.54.

C ₂₃ H ₃₇ NO ₄
Calculated,%: C 70.55; H 9.52; N, 3.58.

Claims (1)

1. The method of obtaining 1-alkyl, 1-alkenyl or 1-alkynaryl-2-amino-1, 3-propanediol of the General formula I
R-

CH

where R is

R ₅ -
CH ₃ (CH ₂ ) _m C

C-
CH ₃ (CH ₂ ) _m CH = CH-, CH ₃ (CH ₂ ) _m CH ₂ -CH ₂ -,

_C-
m is 3-15;
n is 0 to 12;
R ₁ is hydrogen, a group
-C

where R ₆ is hydrogen, lower alkyl, lower alkoxy or a group

_;
R ₂ is hydrogen or lower alkyl;
R ₃ is hydrogen, lower alkyl or a group
-C

,
where R ₆ has the indicated meanings;
R ₄ - group
-C

,
where R ₇ is hydrogen, lower alkyl or CH ₂ OR ₈ , where R ₈ is hydrogen
-C

,
where R ₆ has the indicated meanings,
or R ₁ and R ₈ together with the oxygen atom to which they are bonded form a group of the general formula

where R ₉ and R ₁₀ are independently hydrogen or alkyl,
or its optical isomers, or pharmaceutically acceptable salts, characterized in that a) a compound of general formula II
RCHO,
where R has the indicated meanings;
R ₅ - group
CH ₃ (CH ₂ ) _m C

C-
or

_C-
reacted with a compound of general formula III

where R ₁₁ and R ₁₂ is lower alkyl,
with the receipt of the compounds of General formula I, where R has the indicated meanings, R ₅ is a group
CH ₃ (CH ₂ ) _m C

C-
or

_C-
R ₁ and R ₂ are hydrogen, R ₃ is a COR ₆ group, where R ₆ is lower alkyl and R ₄ is a CO ₂ R ₇ group, where R ₇ is lower alkyl, followed by the isolation of the desired product or b) optionally by reduction alkali metal borohydride in order to obtain the compounds of General formula I, where R has the indicated meanings and R ₅ -
CH ₃ (CH ₂ ) _m C

C-
_or

_C-
R ₁ and R ₂ are hydrogen, R ₃ is an OOR ₆ group, where R ₆ is lower alkyl and R ₄ is a CH ₂ OH group, or c) optionally hydrogenating the compound of general formula I obtained in stage a) or b), in order to obtain the compounds of General formula I, where R has the indicated meanings, where R ₅ -
CH ₃ (CH ₂ ) _m CH ₂ = CH _2
or

R ₁ and R ₂ are hydrogen, R ₃ is COR ₆ , where R ₆ is lower alkyl, and R ₄ is CO ₂ R ₇ , where R ₇ is lower alkyl, or R ₄ is CH ₂ OH, or a) optionally by reduction compounds of General formula I, where R has the indicated meanings, where R ₅ is CH ₃ (CH ₂ ) _n CH ₂ = CH ₂ or

R ₁ and R ₂ are hydrogen, R ₃ is COR ₆ , where R ₆ is lower alkyl, and R ₄ is CO ₂ R ₇ where R ₇ is lower alkyl using alkaline borohydride in order to obtain a compound of general formula I, where R, R ₅ , R ₁ and R ₂ have the indicated meanings, and R ₄ is CH ₂ OH, or l) optionally by hydrogenation of a compound of the general formula I, where R has the indicated meanings, where R ₅ is
CH ₃ (CH ₂ ) _n C

C
_or

_C
R ₁ and R ₂ are hydrogen, R ₃ is COR ₆ , where R ₆ is lower alkyl, and R ₄ is CH ₂ OH, in order to obtain a compound of general formula I, where R, R ₁ , R ₂ and R ₄ have the indicated R ₅ - CH ₃ (CH ₂ ) _n CH = CH or

_,
or f) optionally by hydrolysis of a compound of general formula I, where R is as defined, R ₁ and R ₂ are hydrogen, R ₃ is COR ₆ , where R ₆ is lower alkyl and R ₄ is CH ₂ OH, in order to obtain a compound of general formula I, where R, R ₅ , R ₁ and R ₄ have the indicated meanings, R ₃ is hydrogen, or d) optionally by reacting a compound of the general formula I, where R has the indicated meanings, R ₁ , R ₂ and R ₃ are hydrogen, R ₄ - CH ₂ OH, a lower aldehyde in the presence of a reducing agent to obtain a compound of general formula I, wherein R and R ₅ are as defined above, R ₁ - H, R ₄ - CH ₂ OH, R ₂ and R ₃ - lower Alki Or h) optionally reacting a compound of general formula I, wherein R is as defined above, R _1, R ₂ and R ₃ - is hydrogen, R ₄ - CH ₂ OH, with N-benziloksikarboniloksisuktsinimidom formula

NO

Och

in order to obtain a compound of general formula I, where R and R ₅ are as defined, R ₁ and R ₃ are benzyloxycarbonyl, R ₂ is hydrogen and R ₄ is CH ₂ OR ₈ , where R ₈ is benzyloxycarbonyl, or k) optionally by acylation of the compound General formula I, where R has the indicated meanings; R ₁ and R ₂ are hydrogen, R ₃ is COR ₆ , where R ₆ is lower alkyl, R ₄ is CH ₂ OH, in order to obtain a compound of general formula I, where R, R ₅ , R ₁ , R ₂ and R ₃ have the indicated meanings, R ₄ is CH ₂ OCOR ₆ , where R ₆ is lower alkyl, or l) optionally by reacting a compound of the general formula I, where R has the indicated meanings, R ₁ and R ₂ are hydrogen, R ₃ is COR ₆ , where R ₆ is lower alkyl, R ₄ is CH ₂ OH, with 2,2-dimethoxypropane, in order to obtain a compound of general formula I, where R, R ₂ and R ₃ have the indicated meanings, R ₄ is CH ₂ OR ₈ , R ₁ and R ₈ - taken together form a group of the formula

2. Aldehyde of General Formula III
R ₁ CHO,
where R ₁ -

_,

_,
R ₅ -
CH ₃ (CH ₂ ) _m C

C-
CH ₃ (CH ₂ ) _m CH = CH, CH ₃ (CH ₂ ) _m CH ₂ CH ₂ ,

_C
where m = 3 to 15;
n = 0 - 12,
as an intermediate in the synthesis of 1-alkyl, 1-alkenyl or 1-alkynaryl-2-amino-1,3-propanediols.

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